This overview of reviews summarizes the evidence from systematic reviews (SR) on the effectiveness of antiretroviral therapy (ART) adherence interventions for people with HIV (PWH) and descriptively compares adherence interventions among key populations. Relevant articles published during 1996-2017 were identified by comprehensive searches of CDC's HIV/acquired immunodeficiency syndrome (AIDS) Prevention Research Synthesis Database and manual searches. Included SRs examined primary interventions intended to improve ART adherence, focused on PWH, and assessed medication adherence or biologic outcomes (e.g., viral load). We synthesized the qualitative data and used the Assessment of Multiple Systematic Reviews (AMSTAR) for quality assessment. Forty-one SRs met inclusion criteria. Average quality was high. SRs that evaluated text-messaging interventions ( = 9) consistently reported statistically significant improvements in adherence and biologic outcomes. Other ART adherence strategies [e.g., behavioral, directly administered antiretroviral therapy (DAART)] reported improvements, but did not report significant effects for both outcomes, or intervention effects that did not persist postintervention. In the review focused on people who inject drugs ( = 1), DAART alone or in combination with medication-assisted therapy improved both outcomes. In SRs focused on children or adolescents aged <18 years ( = 5), regimen-related and hospital-based DAART improved biologic outcomes. ART adherence interventions (e.g., text-messaging) improved adherence and biologic outcomes; however, results differed for other intervention strategies, populations, and outcomes. Because few SRs reported evidence for populations at high risk (e.g., men who have sex with men), the results are not generalizable to all PWH. Future implementation studies are needed to examine medication adherence interventions in specific populations and address the identified gaps.