Inappropriate medicine use and polypharmacy create significant challenges for consumers and the health systems they live in, worldwide. In this review, we describe the evidence underpinning interventions directed primarily at healthcare consumers, including information provision, pharmacist-delivered interventions and practical supports, such as reminders to improve outcomes related to medicines. We identify a relatively small number of strategies that seem effective or promising: self-monitoring and self-management programmes, simplified dosing regimens and pharmacist-delivered interventions such as medication review. These interventions could be applied in practice to address some of the problems associated with inappropriate use of medicines, multimorbidity and polypharmacy. The evidence also indicates that success with many strategies is not consistent, suggesting that understanding the individual's context and their preferences will also be important for improving medicines' use. In addition, some strategies in current use are ineffective. Taken together, we argue that the evidence should inform deliberate, rational decisions between strategies to support consumers in using medicines safely and effectively. Future medicine-use research should likewise build rationally and constructively on what is known about promising interventions, avoiding duplication of past research, and working to help consumers negotiate the many challenges presented by polypharmacy.