Recent advances in the manipulation of mouse embryos provide opportunities for the disciplines of neuroscience and molecular genetics to join forces and tackle some previously intractable questions in this area of research. Even Huntington's disease has started to yield clues to its complex pathophysiology as a result of the recent application of transgenic technologies. This short review, while necessarily providing some background clinical information on Huntington's disease, will focus on how modifications of the mouse genome have contributed, and are continuing to contribute, to our understanding of the complex disease process. Such new insights may well turn the hope of developing the first effective treatment for this devastating disease into reality.