This review, updated from the previous version in 2007, aims to assess the effects of interventions designed to enhance medication adherence on both adherence and clinical outcomes. The authors searched multiple databases and included 182 randomized controlled trials (RCTs) with at least 80% follow-up, focusing on interventions that improved adherence and measured both adherence and clinical outcomes. The studies were heterogeneous in terms of patient population, medical conditions, treatment regimens, adherence interventions, and outcome measures. Only 17 RCTs had low risk of bias for both study design and primary clinical outcome, and these studies generally involved complex interventions with multiple components, such as tailored ongoing support from health professionals, education, counseling, and daily treatment support. Despite these interventions, only five RCTs reported improvements in both adherence and clinical outcomes, and no common intervention characteristics were identified. The authors conclude that current methods of improving medication adherence for chronic health problems are complex and not very effective, and more advanced methods are needed, including better interventions, objective adherence measures, and sufficient study power to detect improvements in clinically important outcomes.This review, updated from the previous version in 2007, aims to assess the effects of interventions designed to enhance medication adherence on both adherence and clinical outcomes. The authors searched multiple databases and included 182 randomized controlled trials (RCTs) with at least 80% follow-up, focusing on interventions that improved adherence and measured both adherence and clinical outcomes. The studies were heterogeneous in terms of patient population, medical conditions, treatment regimens, adherence interventions, and outcome measures. Only 17 RCTs had low risk of bias for both study design and primary clinical outcome, and these studies generally involved complex interventions with multiple components, such as tailored ongoing support from health professionals, education, counseling, and daily treatment support. Despite these interventions, only five RCTs reported improvements in both adherence and clinical outcomes, and no common intervention characteristics were identified. The authors conclude that current methods of improving medication adherence for chronic health problems are complex and not very effective, and more advanced methods are needed, including better interventions, objective adherence measures, and sufficient study power to detect improvements in clinically important outcomes.