Some things in general that might help: restart your computer, it will free up any used resources. Quit all other apps. If you are on an Intel Mac, make sure no PowerPC processes are running (see simpleD’s reply above).
I found a Dashboard widget that seemed to be choking my Mac slowly over time (I believe the programmers calls this a “memory leak”). It was also a PowerPC app running on my Intel Mac.
I also recently cleaned up bizarre problems on my Mac by making sure I had all the required System & User fonts activated (I had somehow deactivated some of them).
You can see what fonts are required for 10.4 here: http://support.apple.com/kb/HT1538 and for 10.5 here: http://support.apple.com/kb/HT1642
Also, running the Keychain Repair Utility in the OS X Keychains utility found some errors that I think were slowing down my machine during MobileMe syncs.