diff --git a/cmd/litestream/main.go b/cmd/litestream/main.go
index 0121edf2..1ea4a86d 100644
--- a/cmd/litestream/main.go
+++ b/cmd/litestream/main.go
@@ -290,12 +290,26 @@ func (c *Config) Validate() error {
 	}
 
 	// Validate database configs
-	for _, db := range c.DBs {
+	for idx, db := range c.DBs {
+		// Validate that either path or directory is specified, but not both
+		if db.Path != "" && db.Directory != "" {
+			return fmt.Errorf("database config #%d: cannot specify both 'path' and 'directory'", idx+1)
+		}
+		if db.Path == "" && db.Directory == "" {
+			return fmt.Errorf("database config #%d: must specify either 'path' or 'directory'", idx+1)
+		}
+
+		// Use path or directory for identifying the config in error messages
+		dbIdentifier := db.Path
+		if dbIdentifier == "" {
+			dbIdentifier = db.Directory
+		}
+
 		// Validate sync intervals for replicas
 		if db.Replica != nil && db.Replica.SyncInterval != nil && *db.Replica.SyncInterval <= 0 {
 			return &ConfigValidationError{
 				Err:   ErrInvalidSyncInterval,
-				Field: fmt.Sprintf("dbs[%s].replica.sync-interval", db.Path),
+				Field: fmt.Sprintf("dbs[%s].replica.sync-interval", dbIdentifier),
 				Value: *db.Replica.SyncInterval,
 			}
 		}
@@ -303,7 +317,7 @@ func (c *Config) Validate() error {
 			if replica.SyncInterval != nil && *replica.SyncInterval <= 0 {
 				return &ConfigValidationError{
 					Err:   ErrInvalidSyncInterval,
-					Field: fmt.Sprintf("dbs[%s].replicas[%d].sync-interval", db.Path, i),
+					Field: fmt.Sprintf("dbs[%s].replicas[%d].sync-interval", dbIdentifier, i),
 					Value: *replica.SyncInterval,
 				}
 			}
@@ -461,9 +475,12 @@ type CompactionLevelConfig struct {
 	Interval time.Duration `yaml:"interval"`
 }
 
-// DBConfig represents the configuration for a single database.
+// DBConfig represents the configuration for a single database or directory of databases.
 type DBConfig struct {
 	Path               string         `yaml:"path"`
+	Directory          string         `yaml:"directory"` // Directory to scan for databases
+	Pattern            string         `yaml:"pattern"`   // File pattern to match (e.g., "*.db", "*.sqlite")
+	Recursive          bool           `yaml:"recursive"` // Scan subdirectories recursively
 	MetaPath           *string        `yaml:"meta-path"`
 	MonitorInterval    *time.Duration `yaml:"monitor-interval"`
 	CheckpointInterval *time.Duration `yaml:"checkpoint-interval"`
@@ -533,6 +550,107 @@ func NewDBFromConfig(dbc *DBConfig) (*litestream.DB, error) {
 	return db, nil
 }
 
+// NewDBsFromDirectoryConfig scans a directory and creates DB instances for all SQLite databases found.
+func NewDBsFromDirectoryConfig(dbc *DBConfig) ([]*litestream.DB, error) {
+	if dbc.Directory == "" {
+		return nil, fmt.Errorf("directory path is required for directory replication")
+	}
+
+	dirPath, err := expand(dbc.Directory)
+	if err != nil {
+		return nil, err
+	}
+
+	// Default pattern if not specified
+	pattern := dbc.Pattern
+	if pattern == "" {
+		pattern = "*.db"
+	}
+
+	// Find all SQLite databases in the directory
+	dbPaths, err := FindSQLiteDatabases(dirPath, pattern, dbc.Recursive)
+	if err != nil {
+		return nil, fmt.Errorf("failed to scan directory %s: %w", dirPath, err)
+	}
+
+	if len(dbPaths) == 0 {
+		return nil, fmt.Errorf("no SQLite databases found in directory %s with pattern %s", dirPath, pattern)
+	}
+
+	// Create DB instances for each found database
+	var dbs []*litestream.DB
+	for _, dbPath := range dbPaths {
+		// Create a copy of the config for each database
+		dbConfigCopy := *dbc
+		dbConfigCopy.Path = dbPath
+		dbConfigCopy.Directory = "" // Clear directory field for individual DB
+
+		db, err := NewDBFromConfig(&dbConfigCopy)
+		if err != nil {
+			return nil, fmt.Errorf("failed to create DB for %s: %w", dbPath, err)
+		}
+		dbs = append(dbs, db)
+	}
+
+	return dbs, nil
+}
+
+// FindSQLiteDatabases recursively finds all SQLite database files in a directory.
+// Exported for testing.
+func FindSQLiteDatabases(dir string, pattern string, recursive bool) ([]string, error) {
+	var dbPaths []string
+
+	err := filepath.Walk(dir, func(path string, info os.FileInfo, err error) error {
+		if err != nil {
+			return err
+		}
+
+		// Skip directories unless recursive
+		if info.IsDir() {
+			if !recursive && path != dir {
+				return filepath.SkipDir
+			}
+			return nil
+		}
+
+		// Check if file matches pattern
+		matched, err := filepath.Match(pattern, filepath.Base(path))
+		if err != nil {
+			return err
+		}
+		if !matched {
+			return nil
+		}
+
+		// Check if it's a SQLite database
+		if IsSQLiteDatabase(path) {
+			dbPaths = append(dbPaths, path)
+		}
+
+		return nil
+	})
+
+	return dbPaths, err
+}
+
+// IsSQLiteDatabase checks if a file is a SQLite database by reading its header.
+// Exported for testing.
+func IsSQLiteDatabase(path string) bool {
+	file, err := os.Open(path)
+	if err != nil {
+		return false
+	}
+	defer file.Close()
+
+	// SQLite files start with "SQLite format 3\x00"
+	header := make([]byte, 16)
+	if _, err := file.Read(header); err != nil {
+		return false
+	}
+
+	return string(header) == "SQLite format 3\x00"
+}
+
 // ReplicaConfig represents the configuration for a single replica in a database.
 type ReplicaConfig struct {
 	Type               string         `yaml:"type"` // "file", "s3"
diff --git a/cmd/litestream/main_test.go b/cmd/litestream/main_test.go
index dadbc323..d89b7018 100644
--- a/cmd/litestream/main_test.go
+++ b/cmd/litestream/main_test.go
@@ -622,3 +622,209 @@ func TestConfig_DefaultValues(t *testing.T) {
 		t.Errorf("expected default snapshot retention of 24h, got %v", *config.Snapshot.Retention)
 	}
 }
+
+func TestFindSQLiteDatabases(t *testing.T) {
+	// Create a temporary directory using t.TempDir() - automatically cleaned up
+	tmpDir := t.TempDir()
+
+	// Create test files
+	testFiles := []struct {
+		path       string
+		isSQLite   bool
+		shouldFind bool
+	}{
+		{"test1.db", true, true},
+		{"test2.sqlite", true, true},
+		{"test3.db", false, false}, // Not a SQLite file
+		{"test.txt", false, false},
+		{"subdir/test4.db", true, true},
+		{"subdir/test5.sqlite", true, true},
+		{"subdir/deep/test6.db", true, true},
+	}
+
+	// Create test files
+	for _, tf := range testFiles {
+		fullPath := filepath.Join(tmpDir, tf.path)
+		dir := filepath.Dir(fullPath)
+		if err := os.MkdirAll(dir, 0755); err != nil {
+			t.Fatal(err)
+		}
+
+		file, err := os.Create(fullPath)
+		if err != nil {
+			t.Fatal(err)
+		}
+
+		if tf.isSQLite {
+			// Write SQLite header
+			if _, err := file.Write([]byte("SQLite format 3\x00")); err != nil {
+				t.Fatal(err)
+			}
+		} else {
+			// Write non-SQLite content
+			if _, err := file.Write([]byte("not a sqlite file")); err != nil {
+				t.Fatal(err)
+			}
+		}
+		if err := file.Close(); err != nil {
+			t.Fatal(err)
+		}
+	}
+
+	t.Run("non-recursive *.db pattern", func(t *testing.T) {
+		dbs, err := main.FindSQLiteDatabases(tmpDir, "*.db", false)
+		if err != nil {
+			t.Fatal(err)
+		}
+
+		// Should only find test1.db in root directory
+		if len(dbs) != 1 {
+			t.Errorf("expected 1 database, got %d", len(dbs))
+		}
+	})
+
+	t.Run("recursive *.db pattern", func(t *testing.T) {
+		dbs, err := main.FindSQLiteDatabases(tmpDir, "*.db", true)
+		if err != nil {
+			t.Fatal(err)
+		}
+
+		// Should find test1.db, test4.db, and test6.db
+		if len(dbs) != 3 {
+			t.Errorf("expected 3 databases, got %d", len(dbs))
+		}
+	})
+
+	t.Run("recursive *.sqlite pattern", func(t *testing.T) {
+		dbs, err := main.FindSQLiteDatabases(tmpDir, "*.sqlite", true)
+		if err != nil {
+			t.Fatal(err)
+		}
+
+		// Should find test2.sqlite and test5.sqlite
+		if len(dbs) != 2 {
+			t.Errorf("expected 2 databases, got %d", len(dbs))
+		}
+	})
+
+	t.Run("recursive * pattern", func(t *testing.T) {
+		dbs, err := main.FindSQLiteDatabases(tmpDir, "*", true)
+		if err != nil {
+			t.Fatal(err)
+		}
+
+		// Should find all 5 SQLite databases
+		if len(dbs) != 5 {
+			t.Errorf("expected 5 databases, got %d", len(dbs))
+		}
+	})
+}
+
+func TestIsSQLiteDatabase(t *testing.T) {
+	// Create temporary test files using t.TempDir() - automatically cleaned up
+	tmpDir := t.TempDir()
+
+	t.Run("valid SQLite file", func(t *testing.T) {
+		path := filepath.Join(tmpDir, "valid.db")
+		file, err := os.Create(path)
+		if err != nil {
+			t.Fatal(err)
+		}
+		if _, err := file.Write([]byte("SQLite format 3\x00")); err != nil {
+			t.Fatal(err)
+		}
+		if err := file.Close(); err != nil {
+			t.Fatal(err)
+		}
+
+		if !main.IsSQLiteDatabase(path) {
+			t.Error("expected file to be identified as SQLite database")
+		}
+	})
+
+	t.Run("invalid SQLite file", func(t *testing.T) {
+		path := filepath.Join(tmpDir, "invalid.db")
+		file, err := os.Create(path)
+		if err != nil {
+			t.Fatal(err)
+		}
+		if _, err := file.Write([]byte("not a sqlite file")); err != nil {
+			t.Fatal(err)
+		}
+		if err := file.Close(); err != nil {
+			t.Fatal(err)
+		}
+
+		if main.IsSQLiteDatabase(path) {
+			t.Error("expected file to NOT be identified as SQLite database")
+		}
+	})
+
+	t.Run("non-existent file", func(t *testing.T) {
+		path := filepath.Join(tmpDir, "doesnotexist.db")
+		if main.IsSQLiteDatabase(path) {
+			t.Error("expected non-existent file to NOT be identified as SQLite database")
+		}
+	})
+}
+
+func TestDBConfigValidation(t *testing.T) {
+	t.Run("both path and directory specified", func(t *testing.T) {
+		config := main.Config{
+			DBs: []*main.DBConfig{
+				{
+					Path:      "/path/to/db.sqlite",
+					Directory: "/path/to/dir",
+				},
+			},
+		}
+
+		err := config.Validate()
+		if err == nil {
+			t.Error("expected validation error when both path and directory are specified")
+		}
+	})
+
+	t.Run("neither path nor directory specified", func(t *testing.T) {
+		config := main.Config{
+			DBs: []*main.DBConfig{
+				{},
+			},
+		}
+
+		err := config.Validate()
+		if err == nil {
+			t.Error("expected validation error when neither path nor directory are specified")
+		}
+	})
+
+	t.Run("valid path configuration", func(t *testing.T) {
+		config := main.DefaultConfig()
+		config.DBs = []*main.DBConfig{
+			{
+				Path: "/path/to/db.sqlite",
+			},
+		}
+
+		err := config.Validate()
+		if err != nil {
+			t.Errorf("unexpected validation error for valid path config: %v", err)
+		}
+	})
+
+	t.Run("valid directory configuration", func(t *testing.T) {
+		config := main.DefaultConfig()
+		config.DBs = []*main.DBConfig{
+			{
+				Directory: "/path/to/dir",
+				Pattern:   "*.db",
+				Recursive: true,
+			},
+		}
+
+		err := config.Validate()
+		if err != nil {
+			t.Errorf("unexpected validation error for valid directory config: %v", err)
+		}
+	})
+}
diff --git a/cmd/litestream/replicate.go b/cmd/litestream/replicate.go
index 9d34edd1..23ee20af 100644
--- a/cmd/litestream/replicate.go
+++ b/cmd/litestream/replicate.go
@@ -117,13 +117,24 @@ func (c *ReplicateCommand) Run(ctx context.Context) (err error) {
 		slog.Error("no databases specified in configuration")
 	}
 
-	dbs := make([]*litestream.DB, 0, len(c.Config.DBs))
+	var dbs []*litestream.DB
 	for _, dbConfig := range c.Config.DBs {
-		db, err := NewDBFromConfig(dbConfig)
-		if err != nil {
-			return err
+		// Handle directory configuration
+		if dbConfig.Directory != "" {
+			dirDbs, err := NewDBsFromDirectoryConfig(dbConfig)
+			if err != nil {
+				return err
+			}
+			dbs = append(dbs, dirDbs...)
+			slog.Info("found databases in directory", "directory", dbConfig.Directory, "count", len(dirDbs))
+		} else {
+			// Handle single database configuration
+			db, err := NewDBFromConfig(dbConfig)
+			if err != nil {
+				return err
+			}
+			dbs = append(dbs, db)
 		}
-		dbs = append(dbs, db)
 	}
 
 	levels := c.Config.CompactionLevels()
diff --git a/etc/litestream-directory-example.yml b/etc/litestream-directory-example.yml
new file mode 100644
index 00000000..32e875c5
--- /dev/null
+++ b/etc/litestream-directory-example.yml
@@ -0,0 +1,72 @@
+# Example configuration for replicating entire directories of SQLite databases
+# This configuration demonstrates the new directory replication feature (issue #42)
+
+# Serve metrics over HTTP on port 9090.
+addr: ":9090"
+
+dbs:
+  # Example 1: Replicate all .db files in a directory (non-recursive)
+  - directory: /var/lib/myapp/databases
+    pattern: "*.db"
+    recursive: false
+    replica:
+      type: s3
+      bucket: my-bucket
+      path: myapp/databases
+      region: us-east-1
+
+  # Example 2: Replicate all SQLite files recursively in a multi-tenant directory
+  # Perfect for multi-tenancy where each tenant has their own database
+  - directory: /var/lib/tenants
+    pattern: "*.sqlite"
+    recursive: true
+    replica:
+      type: s3
+      bucket: tenant-backups
+      path: tenants
+      region: us-west-2
+      sync-interval: 1m
+
+  # Example 3: Replicate all database files with multiple replicas
+  - directory: /data/production
+    pattern: "*.db"
+    recursive: true
+    replicas:
+      - type: s3
+        bucket: prod-backups
+        path: databases
+        region: us-east-1
+      - type: file
+        path: /backup/databases
+
+  # Example 4: Mix of directory and single file replication in same config
+  # Single database with specific settings
+  - path: /var/lib/critical/main.db
+    checkpoint-interval: 1m
+    replica:
+      type: s3
+      bucket: critical-backups
+      path: main
+      region: us-east-1
+      sync-interval: 10s
+
+  # Directory of user databases
+  - directory: /var/lib/users
+    pattern: "user_*.db"
+    recursive: false
+    checkpoint-interval: 5m
+    replica:
+      type: s3
+      bucket: user-backups
+      path: users
+      region: eu-west-1
+
+# Global S3 settings (optional)
+# These will be used as defaults for all S3 replicas unless overridden
+access-key-id: ${AWS_ACCESS_KEY_ID}
+secret-access-key: ${AWS_SECRET_ACCESS_KEY}
+
+# Logging configuration
+logging:
+  level: info
+  type: text