They are different from most systems that you would work with on a normal basis, 5250 is a screen at a time protocol, meening that whatever you are filling out (i.e. an order form) is displayed as a full screen, the data you type if buffered, and sent when you hit enter. Standard telnet is charachter at a time: press a key, the keystroke is sent to the server, and echoed back to you. The AS/400 is also where you would run into twinax cabling, to connect dumb terminals, but that is going away in favor of 5250 telnet sessions. Another benefit: No known viruses.
Seeing "Knowledge of AS/400 helpful" and like statements on the job engines and was wondering what this meant.
When you want to know what something is, look it up in the Wikipedia:http://en.wikipedia.org/wiki/AS/400