A systematic review was conducted to identify evidence-based interventions (EBIs) for increasing HIV medication adherence behavior or decreasing HIV viral load among persons living with HIV (PLWH). We conducted automated searches of electronic databases (i.e., MEDLINE, EMBASE, PsycINFO, CINAHL) and manual searches of journals, reference lists, and listservs. Interventions were eligible for the review if they were U.S.-based, published between 1996 and 2011, intended to improve HIV medication adherence behaviors of PLWH, evaluated the intervention using a comparison group, and reported outcome data on adherence behaviors or HIV viral load. Each intervention was evaluated on the quality of study design, implementation, analysis, and strength of findings. Of the 65 eligible interventions, 10 are EBIs. The remaining 55 interventions failed to meet the efficacy criteria primarily due to null findings, small sample sizes, or low retention rates. Research gaps and future directions for development of adherence EBIs are discussed.