As the empirical method and the double-blind, randomized trial came to dominate medical research, the menstrual cycle and the possibility of pregnancy disqualified female subjects from most investigations— pregnancy because of the possibility of teratogenicity, and the menstrual cycle because it might complicate research findings. In 1993 the U.S. Congress mandated the inclusion of women in clinical trials. It is now essential that we look at gender differences in order to ensure that the treatments developed before 1993 work as well for our female patients as for the male patients on whom they were tested. Gender differences do complicate research, but they also offer a window into physiological and pathophysiological processes and raise questions that inform new research directions. Since the menstrual cycle, menopause, and administration of hormones, including oral contraceptives and exogenous "replacements" later in life, affect nonreproductive functions, including blood levels of psychopharmacologic agents, their effects tell us something about how those agents work. If men’s and women’s brains bind opioids differently, we may be able to use that difference to explore the process of opioid binding. If men and women react differently to traumatic early experiences, we may come to understand where and how a traumatic experience is handled, both in the psyche and in the central nervous system.