Recent progress in our understanding of Rett syndrome has been dramatic. Against the background that the clinical features of Rett syndrome may be reversible, in part or in whole, substantial optimism has emerged regarding possible therapies. As such, it is timely to update recent research progress. This update summarizes research advances during the past 18 to 24 months in terms of clinical and translational research, as well as basic research. © SAGE Publications, Inc. 2008.