Sex differences in drugs are well documented to be understudied. Nevertheless, a considerable body of knowledge exists about sex differences in drugs. This article presents an overview of sex differences in drugs and provides directions for future research and clinical care. The term sex differences subsumes four separate but overlapping concepts that are often used interchangeably but should be distinguished: sex (male or female), gender (socially or culturally constructed variable), sexuality (sexual feelings, thoughts, and behaviors), and reproductive function (reproductive system, menstrual cycle, menopause, etc). Sex differences in drugs may be due to differences in pharmacokinetics (delivery of the drug to the site of action and away from it) or pharmacodynamics (drug effects at the site of action, including receptor activity and second and subsequent messengers) and may be related to sex differences in physiological factors, prevalence or expression of pathophysiologic factors, comorbidity with conditions with greater prevalence in one sex, or drug interactions with drugs taken more commonly by one sex. The article provides an overview of sex differences in pharmacokinetics and presents results of a study that found that varying antidepressant dosing over the course of the menstrual cycle optimized treatment in a subset (about one quarter) of women with depressive symptoms related to the menstrual cycle. Also presented is an overview of sexual side effects of drugs in women and men and current approaches to treatment, including the conservative approach, drug substitution, drug holidays, and supplemental medication. Finally, the Food and Drug Administration's new guidelines for inclusion of women in clinical trials are briefly reviewed, including variables that the Administration recommends should be studied.