Innovations in synthetic chemistry have enabled the discovery of many breakthrough therapies that have improved human health over the past century. In the face of increasing challenges in the pharmaceutical sector, continued innovation in chemistry is required to drive the discovery of the next wave of medicines. Novel synthetic methods not only unlock access to previously unattainable chemical matter, but also inspire new concepts as to how we design and build chemical matter. We identify some of the most important recent advances in synthetic chemistry as well as opportunities at the interface with partner disciplines that are poised to transform the practice of drug discovery and development.