I don't have a Mac, but my landlady has two of their notebooks, and occasionally asks for my help. Recently she had problems with applications such as Safari just not starting at all, so I looked in to it, and I thought I should report what I found in case it helps anyone:
MacBook Pro, about 5 y.o.
OS X Tiger 10.4.11. Yes, I know, and so does she, but her "Mac guy" does that kind of thing. If he can be contacted. I suspect he may be replaced by me at some point in the future.
Microsoft Office 2007 for Mac, up-to-date.
The basic problem had happened before and was known: the hard disk drive was completely full, with 0KB free, and that stops e.g. Entourage from starting with an obscure error about caches. She had previously removed unnecessary applications and archived photos, but it kept happening. To find out where the space was going, I persuaded her to let me open a terminal and run a few commands such as "df" and "du". (I'm a Linux user, and it's all UNIX anyway.)
I found that her Caches folder was taking up a several GB of space, and after some online research, I found that some subfolders could be safely removed. Safari cache, for example. After that and a couple more application removals, there was about a GB free and she could work ... but the disk was thrashing, and we could see the free space dropping like a plane after a bird strike.
More digging commands, and I could see that there was over 1.5GB in an Entourage cache folder. This was an index that Entourage was creating of all her mail. Of which there was plenty, and that was what was filling up the hard drive. It's a setting that Entourage has that indexes mail so it can be found by Spotlight, the OS X indexing system.
She never used Spotlight seriously, she said, so I turned it off in Entourage preferences, and that deleted its index - freeing up almost 2GB of disk in minutes. Then turned Spotlight off entirely and deleted the index (more terminal commands).
So the machine's a lot happier without all that indexing thrashing the disk and filling it up. Turns out that the Entourage Spotlight indexing process is so dumb, it will completely fill up the hard drive to the last byte, which stops Entourage from loading at all.
And if anyone wants to tell me I didn't do things "the Apple way", well ... this problem wasn't Apple's fault, and (in any case) I'm not a Mac person, I only care about getting things to work. Sorry ..!
* three if you include the PowerMac G3 laptop in the attic!