Work with images on external drives (or similar) that you can unplug and turn off.
There are several reasons for this, but you don't want gobs of images cluttering up your PCs hard drive and messing up its backups, fragging the hard drive, etc, etc. Also when the PC fails you'll still have easy access to the images. This has just happened to me BTW.
Make sure you have a good backup strategy where the incremental backups are fast and efficient. That way you can do them after every few hours of work rather than once a week.
The time an incremental backup takes should be proportional to the amount of work you've done. Make sure whatever you use can be recovered from - test it. I've used several backup utilities that are very difficult to recover from and get things back to exactly where they were before. Don't assume that just because a backup utility is a market leader that it is working for you. Make sure that the backup you use does not keep old copies of images as you change them, and keeps master originals. Otherwise you'll waste space or accidentally lose images.
Personally, I stay away from keeping images as TIFFs or PSDs as part of my mainstream automated workflow as they will waste much space.
Make sure you have a good image naming convention that will survive contact with a long time. I name my files "Date""time""version", and use Apple Aperture to generate such file names. I've tested it and can't break it's algorithm to mess up and overwrite one file with another file of the same name. DownloaderPro also has reasonable file naming conventions built in, although the program is not so bullet proof. I use databases to find files, as others have mentioned.
On another note, storage solutions keep increasing in size, so if you are generating images at a fairly constant rate, you can figure out the future storage needs and see whether your method is going to break a year or 2 down the line. For example, if you started with 80GB drives a few years ago, you could now switch to 750GB drives, or 1.5 TB raid 0. Maybe in that time frame you haven't generated that many images! It's a lot easier to do a large file copy every few years to upgrade hard drives than to keep futzing around with CDs/DVDs or many hard drives every few days.
If you think all of this is hard, wait until you try video.
--len