[Backpack](http://www.backpackit.com/) from 37Signals is a great PIM, I use it myself. infiniteNIL has released [PackRat 1.1](http://www.infinitenil.com/packrat), a desktop client to manage your Backpack data when you're offline. This new version includes Applescript support and a handy Automator action, *Synchronize with Backpack*, allowing you to schedule synchronization when you're back on the grid. (via [MacMinute](http://www.macminute.com/)).