I have two setups with three monitors. One at work and one at home. Both use two desktops. Home is two 24" at 1920x1200, along with a 20" at 1680x1050. Work is three 20" at 1680x1050. The third monitor is on the second machine, and is accessible via synergy. The third monitor is great for IM, especially for work related stuff. I can look at it at a glance, along with a spreadsheet on the second monitor, and four terminal windows on the first monitor.
At home the second desktop is another Linux box that I use for additional storage for the primary desktop via iSCSI. At work the second desktop is a Windows machine.
I only recently went to three monitor. I looked at doing it with a second video card in the main desktop, or using a Matrox splitter box to run two monitors off one DVI connector. A second video card in Linux just doesn't work that well, and the splitter boxes are expensive. Plus a second computer has some advantages. More segregated CPU and memory, more storage, different OS, etc.