* Things like progressive enhancement and semantic markup might not be totally impossible, but they're definitely not the focus of the framework.
* The back button is broken by default; there's a work-around but you're probably used to getting that functionality for free.
* The GWT compile cycle is LONG.
* You pretty much NEED to be using Eclipse (or possibly IntelliJ) instead of your text editor of choice.
* The final product probably won't feel like most web applications.
To be fair, people have written things like [quake2-gwt](http://code.google.com/p/quake2-gwt-port/), so you can get something pretty awesome in exchange for these tradeoffs. Also, if you loathe HTML and JavaScript, but you still need to get something up on the web, then GWT might be just your ticket.