In 2020 the Drug Hunter site highlighted >150 “molecules of the month” whose structures or stories were typically published for the first time. They were selected from thousands of research articles, published by leading institutions around the world. It was incredibly hard to narrow down the selection to just one molecule from each month, and it’s agonizing to leave so many amazing stories off this list, but here are 12 molecules from 2020 that our community would likely all agree we learned a lot from. The molecules were selected based on a range of factors, from clinical and commercial timeliness (such as Mirati’s market-moving KRAS inhibitor from April) to mechanistic proof of concept (such as GSK’s RIPK2 degrader with prolonged PD) to interesting modalities (such as Novartis’s reversible-covalent aldehyde FGFR4 inhibitor) to overcoming a brutal drug discovery campaign against a difficult mechanism of action (such as Gilead’s HIV capsid inhibitor).