Be in the know that "all" programs & even the OSX system use Virtual Memory (VM) which means they store memory on the HDD. So when you're running programs you'll find the available space on your startup disk diminishes temporarily whilst those programs are open. Answer? If you have other drives, move your documents & even some of the non apple programs over to it. I now run with only a minimal no. of programs actually stored on the startup disk. But then I have 2 HDD's divided up into 7 partitions. If you can't manage to move programs then move some of your non-compulsory documents off the drive & onto backup.

eg: I also have several external firewire drives. One of them contains my iTunes library & the iTunes program.