Background <p>“Shelf-life” or “expiration dating period” aims to ensure that medicines retain the quality, safety and efficacy parameters throughout that time span. After expiry, medicines become pharmaceutical waste that leads to decreased availability of healthcare products, financial losses and environmental pollution. Increasing evidence shows that medicines stay stable and effective long after their labelled expiry dates.</p> Objectives <p>This review was conducted to highlight the stability and effectiveness of medicines beyond the expiration dates granted during the marketing authorization review process.</p> Methods <p>This review was registered in PROSPERO (CRD42024629089). Five databases (PubMed, Embase, Web of Science, Scopus, Google Scholar) were searched from inception to 15 December 2024. 43 studies met the inclusion criteria. Risk-of-bias was not formally assessed.</p> Results <p>A total of 8125 articles were retrieved, out of which 43 met the criteria for final inclusion. The included articles represent 3786 samples of expired products, of which 89.1% were found stable after expiry or had their shelf-life extended. Four samples were noted to be clinically effective after expiry, although mild side effects were reported occasionally.</p> Conclusions <p>Many medicines remain stable and effective well beyond their labeled expiration dates, indicating a need to reconsider current shelf-life assignment practices. Extending shelf-lives should be evaluated to minimize pharmaceutical waste and increase medicine access. The final decision to use expired medicines or extend their shelf-life should rest with medicine regulatory agencies after risk-based consideration of available evidence, individual product characteristics and patient safety. The use of expired medicines outside regulatory oversight is not endorsed. The findings provide a rationale for evidence-based shelf-life reassessment.</p>