One option would be to just use launchd. Save a property list like this as ~/Library/LaunchAgents/com.superuser.445907.plist, and load it with launchctl load ~/Library/LaunchAgents/com.superuser.445907.plist or by logging out and back in.
<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE plist PUBLIC -//Apple Computer//DTD PLIST 1.0//EN
http://www.apple.com/DTDs/PropertyList-1.0.dtd>
<plist version="1.0">
<dict>
<key>Label</key>
<string>com.superuser.445907</string>
<key>Program</key>
<string>/Users/username/script</string> <!-- ~/ doesn't work -->
<key>WatchPaths</key>
<array>
<string>/Users/username/Folder/</string>
</array>
<key>ThrotteInterval</key>
<integer>0</integer> <!-- run at most every 0 seconds, by default 10 -->
</dict>
</plist>
Launchd only registers changes to files when they are saved atomically, or deleted and recreated every time they are saved. Most OS X applications perform atomic saves by default, but for example TextMate and vim don't. Changes in subfolders of watched folders aren't detected.
launchctl unload $path && launchctl load $path applies changes to a plist.
See man launchd and man launchd.plist for more information.