Despite 20 years of intensive studies after the discovery of the first-in-class small-molecule inhibitor, Nutlin-3, no drugs targeting MDM2-p53 interaction have reached the market. Nevertheless, more than 10 compounds are still being evaluated in clinics, both as standalone drugs and in combinations with other targeted therapies or standard chemotherapy agents, including two inhibitors in phase 3 studies and two compounds granted orphan-drug/fast-track designation by the FDA.