Introduction: This overview aimed to find, assess, and synthesize systematic reviews that compared the cost-effectiveness of interventions designed to improve medication adherence among patients with chronic disease.Areas covered: PubMed, Web of Science, Cochrane Database of Systematic Reviews, and Center for Review and Dissemination were searched. The quality of the included reviews was assessed using two validated checklists. The review characteristics and findings were summarized narratively. A total of 9 systematic reviews were included. Interventions reported to be cost-effective were simplification of the medication regimen, financial incentives, improved coverage or reduced out-of-pocket spending, and pharmacist care. The most common interventions were patient education and counseling, with mixed results of cost-effectiveness. This evidence comes from economic evaluations with varying degrees of quality.Expert opinion: Future evaluations of adherence interventions' cost-effectiveness will be improved in quality as our understanding of the reasons behind intentional and unintentional nonadherence and factors associated with this behavior advances. The development of criteria for the value assessment of medication adherence-enhancing interventions will contribute to improving the quality of adherence intervention cost-effectiveness research.