Even in wealthy economies, access to medicines is increasingly affected by medicine shortages – an issue exacerbated with the onset of the COVID-19 pandemic. The aim of this paper was to examine the extent and nature of medicine shortages in OECD countries (pre-COVID-19) and explore the reasons for this growing global problem. Although differences in monitoring mechanisms make multi-country analyses challenging, a sample of 14 OECD countries reported a 60% increase in the number of shortage notifications over the period 2017-2019. While the complexity of pharmaceutical manufacturing and supply chains hampers root cause analyses, available literature suggests that shortages, as reported by marketing authorisation holders, are predominantly due to manufacturing and quality issues. Nevertheless, commercial factors - and the policy settings that influence them - may play an important role. Although several OECD countries have implemented policy measures to mitigate, monitor and prevent shortages, more robust data and further analyses of root causes and effective policy responses are needed. The way forward should involve a global approach that engages all relevant actors and looks beyond the health care sector alone.