I assume you are talking about installing your software on the external drive instead of internal drive. Can't just move them, have to reinstall them.
It would probably work in most cases, but expect problems. Obviously the application won't be there when the drive isn't plugged in. With some programs, that could give you grief even if you don't intend to run the program. Also, USB is slower than IDE and SATA, so the program won't perform as well as it should.
So if you are running out of space, buy a new internal hard drive or add a second hard drive instead. They're sometimes cheaper than the external ones, and faster. And after the initial hassles of installing them, they're much less trouble.
Edited by jds63, 02 October 2014 - 06:08 PM.