Changes in the clinical management of women living with human immunodeficiency virus (HIV) have occurred as a result of significant gains in the scientific knowledge of this retrovirus. As the incidence of HIV/AIDS continues to escalate among female adults and adolescents in the United States, all primary health care providers must anticipate the likelihood of encountering clients with HIV infection. Midwives must be adequately prepared to meet the challenges of managing women with HIV in the early stages of the disease. This article presents a comprehensive review of current demographic trends related to the HIV/AIDS epidemic among U.S. women and a brief overview of the essential immunopathogenesis of HIV. Contemporary issues related to universal counseling, updated testing procedures, and reproductive decision-making are covered. Initial primary care concerns and the management of newly infected seropositive women are included, with a focus on gynecologic issues. Guidance in the current management of HIV-positive pregnant women is offered. Updated antiretroviral prophylaxis recommendations are presented, to prevent perinatal transmission and to delay maternal immunosuppression with subsequent opportunistic infections. The article concludes with implications for health care professionals who provide care for this unique cohort of women.