An abundance of recent research indicates that there are multiple differences between males and females both in normal physiology and in the pathophysiology of disease. The Refresher Course on Gender Differences in Physiology, sponsored by the American Physiological Society Education Committee at the 2006 Experimental Biology Meeting in San Franciso, CA, was designed to provide teachers of medical physiology with the background necessary to include the most important aspects of sex-based differences in their curricula. The presentations addressed sex-based differences in the physiology and pathophysiology of the cardiovascular, musculoskeletal, and immune systems as well as the cellular mechanisms of sex steroid hormone actions on nonreproductive tissues. The slides and audio files for these presentations are available at http://www.the-aps.org/education/refresher/index.htm. This overview highlights the key concepts relevant to the topic of sex-based differences in physiology: why these differences are important, their potential causes, and examples of prominent differences between males and females in normal physiological function for selected organ systems.