To set it up, you log into the Harmony Remote web site, tell it which components you have, then download a configuration file which is uploaded to the remote via a USB cable. It’s prettty darn slick. It even works with my Dish Network DVR/receiver which has a UHF remote but (luckily) also accepts commands via IR.
It has ‘mode’ buttons along the top; you select what you want to do (watch TV, watch a DVD, listen to music) and it turns on all the appropriate components and changes their settings accordingly. This is exactly what I was looking for, so far so good.