kckrug1994 asked the Answer Line Forum if a game or application would will work if installed onto an external drive.
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 EISA and SATA, so the program won't perform as well as it should.
But why do you want to put a program on an external drive?
If it's because you're running out of space, buy a new internal hard drive, instead. They're cheaper than the external ones, and faster. And after the initial hassles of installing them, they're much less trouble.
If you want to easily run that program on multiple computers, use a portable program designed for that purpose. And strictly speaking, these don't need to be installed, just copied. Wikipedia has a list of portable software, although I don't know how up-to-date it is.