AIDS is essentially the same disease in men and women, but a combination of social, psychological, and physiologic factors appear to define HIV disease and AIDS in women and suggest that different approaches may be needed for female patients. The likelihood that a woman will receive, adhere to, and respond to antiretroviral therapy differs from that among men. Specific psychosocial issues serve as barriers to treatment and adherence in women. Gender differences in CD4+ counts and viral load may warrant revisions of standard treatment guidelines, which were originally developed for men. Physicians need to understand gender differences in the course of AIDS, treatment responses, and the efficacy of newer antiretroviral drugs. Earlier diagnosis of HIV infection and AIDS in women may hinge on recognition of gender-specific AIDS-defining illnesses. Development of once-daily, tolerable, safer pharmacologic agents with distinct resistance profiles might improve adherence and efficacy of treatment in both men and women.