It depends on what language you're using and your requirements, but my preference is Qt. It has bindings to several languages; it supports most common platform

It depends on what language you're using and your requirements, but my preference is Qt. It has bindings to several languages; it supports most common platforms; the API is consistent, stable, and well documented; and it's easy to get up and running on all of the platforms it supports. One complaint people have about Qt is that it doesn't "look native" enough. That's not something I personally care about, and it's not a problem at all for the applications I write, but it's an issue for some people. IME, that's just a trade off of using a cross-platform GUI library. If the layout is good and it's easy to use, most people won't care if it doesn't look native. Photoshop doesn't "look native" either, yet it has a huge following and brings in a ton of money.