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I am currently working on automated GUI tests for an application, and Sikuli looks pretty great -- even when compared to enterprise level automated GUI testing tools costing in the order of thousands of dollars per user licence.
Some of the commenting below on maintainability problems seem pretty superficial. For example, to ease maintainability you could build a framework abstracting GUI component images from regression test scripts. For example, you could assign a screenshot as a variable and then refer to that variable throughout your test, so if a button happens to change dramatically, you make the change in potentially one place in your code instead of every time it is used in a click. The fact that the tool appears simple (not too many bells and whistles) and is based on Python seems to be major advantages for maintainability.
Check out this interesting academic paper which specifically addresses using Sikuli for automated GUI testing: "GUI Testing Using Computer Vision, CHI 2010" at http://sikuli.csail.mit.edu/documentation.shtml
Has anybody actually used Sikuli? I'd be very curious if anybody has used this for automated GUI testing in a corporate environment...