In the early years of the HIV epidemic, the burden of the disease was principally among men. In recent years, HIV infection among women has become a growing problem worldwide. There is now an increasing awareness that HIV may affect men and women differently. New data have emerged from studies that have focused on HIV-infected women, suggesting the existence of sex-related differences in natural history, pharmacokinetics, and toxicity of antiretroviral therapy. This paper reviews the current literature with an emphasis on recent data regarding sex differences in HIV that have implications for clinical practice.