Is there a guideline for the max number of active fonts I manage my fonts through FontExplorer X. Today I noticed that I have 770 fonts activated. All legitimately licensed, by the way. The Adobe CS family installs a bunch, I've purchased and have received many more from friends: I could easily activate a 1,000+ fonts. (I'm referring to individual font files, not 1,000 font families).

At different times I've heard that it's not a good practice to have too many fonts active at once, but I can't find any guidelines as to what constitutes too many, and I really don't understand where the overhead is spent. Is it simply the font-listing UI's in different apps, or does every active font actually bring some overhead at a general OS performance level?

Let me know if my inquiry is unclear.
I would say you are the slowest part of the equation in most cases. If you find yourself slowing down since you have too many choices, slim down your fonts. If not, don't worry until you notice a program you need to be responsive lagging.

On the CPU side, any computer will track 10,000 files as easily as it tracks 1. Unless you have software that is really poorly programmed and refuses to render a font menu until it loads a sample of each of the 1000 font faces - you'll likely not ever notice a slow down. No one cleans out their iTunes library since there are 10,000 or 40,000 music files since you never access them all at once. The smart programmer makes an ordered list to hold the playlists and only references the files when you need to play a specific song.

You can test this yourself by opening a word processor and a spreadsheet and open the font picker. Time how fast it loads and then go in and deactivate 900 of the font faces and repeat the measurement.

You'll probably have slowness the first time the program or the OS has to traverse the list of active fonts and do some caching. After that, the speed to open the UI should be basically constant whether you have 100, 1000 or 10000 items to load.