Purpose To demonstrate that whereas all HIV-infected youth evidence complex factors that challenge retention in care and adherence to treatment, HIV-infected females have additional issues that are gender-specific. Methods Preliminary data from a subset of 21 adolescent/young women under age 25 from the Whole Life mental health-perinatal HIV care project were analyzed to illustrate the needs of these patients. Results Of the 21 young women assessed, all but one was of minority background, and a sizeable majority had limited education (<high school diploma) and were quite poor (incomes <$500/mo.). Nearly 67% first learned of their HIV status between ages 16 and 19 years. More than three-fourths were pregnant and, of these, more than one-third entered prenatal care in the last trimester. More than half had responsibility for one to two other children. Two-thirds reported having unprotected sex in the prior 6 months. Nearly 43% had CD4 counts of 500 or below. About one-third screened positive for a mental health problem, and the majority reported a striking frequency of exposure to abusive events and traumatic losses across their short lifetimes. Conclusions Adolescent girls and young women have unique needs for developmentally appropriate medical and psychosocial approaches to promote retention and adherence.