Sex differences in the pharmacologic effects of antiretroviral drugs are increasingly being reported. Emerging evidence suggests that women may be at increased risk of developing adverse effects of antiretroviral drugs. Several mechanisms have been proposed to explain sex differences in drug effects, including physiologic differences between men and women and the influence of sex hormones on drug metabolism. This article reviews sex-related variations in the levels of expression and activities of drug transporters and metabolizing enzymes involved in the disposition of the antiretroviral drugs, and postulates that these variations may partly explain sex differences in the responses to these drugs. Studies that explore relationships between levels of expression and activities of relevant enzymes and drug transporters and observed sex-related differences in treatment responses to antiretroviral drugs will help clarify the extent to which molecules involved in drug disposition affect sex differences in treatment response.