Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which are published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules. In these Editorials, we highlight, in brief reports of about one hundred words, a number of recently published articles that describe crucial findings such as the discovery of novel drug targets and mechanisms of action or novel classes of drugs, and may inspire future medicinal chemistry endeavors devoted to address prime unmet medical needs.