OS 10.5 - Force Quit Won't Work/Epic Lock Ups

So I just recently started having trouble with my Macbook Pro involving applications locking up, and then not being able to force quit. Oh, they pretend to force quit. In fact they show dialogues saying they've quit, and their windows disapear, however in the force quit box, the cmd+tab window, and the dock the apps are all still there.

If I try and do a force quit again from the dock, the finder locks up.

The only fix is to force my computer to reboot, which cannot be healthy doing so much.

Other weird bugs is that once I do this forced shutdown/reboot my external drives will be missing files I previously moved to them (say I moved from drive a to b, after this forced reboot they'll be back on a and not on b)

The only thing I can think that's causing it is I have an external drive that's been acting up and I didn't start having this problem until the drive starting acting up... but I wouldn't think they're related!

Any ideas? I don't want to destroy my computer!

Running OS 10.5.6
2.4 GHz Intel Core 2 Duo
2 gb 667 MHz DDR2 SDRAM
Macbook Pro