there are marked differences between men and women in the incidence and expression of many major disease entities (8, 9). These sex-based1 differences in the pathophysiology of disease imply, in turn, that there are important underlying differences in physiological function. Despite the importance of this topic, sex-based differences in physiology are typically not systematically addressed either in physiology textbooks or in the medical physiology curriculum, with the obvious exception of reproductive physiology. For this reason, the Americal Physiological Society (APS) Education Committee elected to address this topic for the Refresher Course presented at the 2006 Experimental Biology Meeting in San Francisco, CA.Until recently, most basic and clinical research either was performed exclusively in male subjects or included both sexes but did not differentiate between males and females in the data analysis. This reflected the broad assumption that there are minimal differences in the physiology and pathophysiology of males and females other than those that specifically involve the reproductive system. The potential complexities of controlling for the various phases of female reproductive cycle served as an additional deterrent for the inclusion of females in experimental design for both animal and human studies. During the period of 1977–1993, furthermore, women of reproductive age were required to be excluded from phase I clinical trials because of concerns about potential teratogenic effects. Since that time, there has been a progressively increasing emphasis on the inclusion of women in clinical trials as well as statistical analyses that specifically evaluate possible sex differences (8).