Adolescents with HIV are at high risk for suboptimal adherence but have been ignored by the literature. Treatment outcome and feasibility data for the first-known adaptation of Behavioral Family Systems Therapy (BFST) targeting adherence among adolescents with HIV are presented for four adolescents with suboptimal adherence. The intervention was delivered in an alternating home-based and telehealth format and a multi-method adherence assessment approach was used. Adherence improved for three adolescents, viral load decreased for two adolescents, and barriers to adherence declined for all participants. Delivery of an adapted BFST intervention was acceptable to families and may be a promising treatment approach.