Highlights • Systematizing medicinal chemistry knowledge can make it evidence based and identify valuable exceptions to established medicinal chemistry dogma. • There is a huge amount of unique medicinal chemistry knowledge. • Evidence based medicinal chemistry can counter individual and team biases. • IP sensitive medicinal chemistry knowledge can be exchanged securely by using context dependent matched molecular pair analysis. • The corporate ecosystem of drug discovery is the last barrier to knowledge sharing. It is both the best of times and the worst of times to be a medicinal chemist. Massive amounts of data combined with machine-learning and/or artificial intelligence (AI) tools to analyze it can increase our capabilities. However, drug discovery faces severe economic pressure and a high level of societal need set against challenging targets. Here, we show how improving medicinal chemistry by better curating and exchanging knowledge can contribute to improving drug hunting in all disease areas. Although securing intellectual property (IP) is a critical task for medicinal chemists, it impedes the sharing of generic medicinal chemistry knowledge. Recent developments enable the sharing of knowledge both within and between organizations while securing IP. We also explore the effects of the structure of the corporate ecosystem within drug discovery on knowledge sharing.