I convinced my 60+ year old parents to get one and they set it up without my help. Thats how easy it is.
Logitech have a nice database of devices, and all of mine were already in there so there was not much fiddling around to do.
Even with NowTV for example, the remote has the 4 colour buttons on it and they all work the same as the original Now remote. The INFO, MENU buttons, program guide, favourites, subtitles, and all buttons just worked straight away out of the box without doing anything. Some buttons that are specific to NowTV (therefore are not hard buttons on the logitech remote) showed up automatically on the LCD panel of the remote.
The same with all my other devices. With my Sony 5.1 receiver, it knew all the advanced buttons like how to change the sound field, etc.
I only had one problem out of the box and that was that it could not turn off the NowTV decoder for some reason. But the remote has a "learning" port so I pointed the original NowTV remote at it and trained the logitech how to turn off the NowTV box properly.
I also trained the remote how to turn on/off the aircon while it is in the middle of another "activity" and things like that.
I was surprised how quick and easy it was to set up. I thought I would be spending weeks getting it right.