Book excerpt: Cancer is the second leading cause of death. Every year, many anticancer drug candidates are discovered and synthesized, but the major challenge lies in identifying, characterizing and evaluating their efficacy. The aim of this Research Topic, "New Mechanisms for Anti-Cancer Drugs" is to collect a group of publications focused on novel chemical compounds exhibiting new modes of actions and/or new target proteins to fulfill their cytotoxic activity on cancer cells. In this context, we will also be pleased to consider studies on drug repurposing, including approved, discontinued, and shelved drugs, when anti-cancer activity results from an unexpected mode of action.