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Objectives: To assess the effectiveness of patient, provider, and systems interventions (Key Question [KQ] 1) or policy interventions (KQ 2) in improving medication adherence for an array of chronic health conditions. For interventions that are effective in improving adherence, we then assessed their effectiveness in improving health, health care utilization, and adverse events., Data Sources: MEDLINE®, the Cochrane Library. Additional studies were identified from reference lists and technical experts., Review Methods: Two people independently selected, extracted data from, and rated the risk of bias of relevant trials and systematic reviews. We synthesized the evidence for effectiveness separately for each clinical condition, and within each condition, by type of intervention. We also evaluated the prevalence of intervention components across clinical conditions and the effectiveness of interventions for a range of vulnerable populations. Two reviewers graded the strength of evidence using established criteria., Results: We found a total of 62 eligible studies (58 trials and 4 observational studies) from our review of 3,979 abstracts. These studies included patients with diabetes, hyperlipidemia, hypertension, heart failure, myocardial infarction, asthma, depression, glaucoma, multiple sclerosis, musculoskeletal diseases, and multiple chronic conditions. Fifty-seven trials of patient, provider, or systems interventions (KQ 1) evaluated 20 different types of interventions; 4 observational studies and one trial of policy interventions (KQ 2) evaluated the effect of reduced out-of-pocket expenses or improved prescription drug coverage. We found the most consistent evidence of improvement in medication adherence for interventions to reduce out-of-pocket expenses or improve prescription drug coverage, case management, and educational interventions across clinical conditions. Within clinical conditions, we found the strongest support for self-management of medications for short-term improvement in adherence for asthma patients; collaborative care or case management programs for short-term improvement of adherence and to improve symptoms for patients taking depression medications; and pharmacist-led approaches for hypertensive patients to improve systolic blood pressure., Conclusions: Diverse interventions offer promising approaches to improving medication adherence for chronic conditions, particularly for the short term. Evidence on whether these approaches have broad applicability for clinical conditions and populations is limited, as is evidence regarding long-term medication adherence or health outcomes.