Sure, it'll work. The Harmony remotes can communicate with any device that has an IR sensor so long as you program it properly.
You can either try and download some preset codes from Logitech, which covers an impressive array of devices, or you can have your Harmony remote capture the signal from the device's original remote.
I use my Harmony 659 to control my source selector, audio receiver, and Xbox... So at a press of a button, I can have them all configured for use with Xbox Media Center... My source selector is set to the right input, volume controls are mapped to my audio receiver, and the majority of the other controls are left to my Xbox. So much nicer than having 2-3 remotes nearby at all times.
Tom Merritt did a Quick Tips episode showing how to set up your Harmony remote to control DVD playback on the XBOX360, by configuring your remote to operate a media center PC.... COOL! My question is, will this work on the PS3 as well? AND, will this work on the XBOX if I add the optional HD-DVD (or future BluRay - fingers crossed) player?