Nearly 2 billion people globally have no access to essential medicines. This means essential medicines are unavailable, unaffordable, inaccessible, unacceptable or of low quality for more than a quarter of the population worldwide. This supplement demonstrates the implications of poor medicine access and highlights recent innovations to improve access to essential medicines by presenting new research findings from low- and middle-income countries (LMICs). These studies answer key questions such as: Can performance-based financing improve availability of essential medicines? How affordable are cardiovascular treatments for children? Which countries' legal frameworks promote universal access to medicines? How appropriately are people using medicines? Do poor-quality medicines impact equity? Answers to these questions are important as essential medicines are vital to the Sustainable Development Goals and are central to the goal of achieving Universal Health Coverage. Access to affordable, quality-assured essential medicines is crucial to reducing the financial burden of care, preventing greater pain and suffering, shortening the duration of illness, and averting needless disabilities and deaths worldwide. This supplement was organized by the Medicines in Health Systems Thematic Working Group of Health Systems Global, a membership organization dedicated to promoting health systems research and knowledge translation. The five studies in the supplement further our understanding by showcasing recent successes and challenges of improving access to quality-assured medicines through health systems in LMICs.