Carbon nanotubes (CNTs) are the most studied allotropic form of carbon. They can be used in various biomedical applications due to their novel physicochemical properties. In particular, the small size of CNTs, with a large surface area per unit volume, has a considerable impact on their toxicity. Despite of the use of CNTs in various applications, toxicity is a big problem that requires more research. In this Review, we discuss the toxicity of CNTs and the associated mechanisms. Physicochemical factors, such as metal impurities, length, size, solubilizing agents, CNTs functionalization, and agglomeration, that may lead to oxidative stress, toxic signaling pathways, and potential ways to control these mechanisms are also discussed. Moreover, with the latest mechanistic evidence described in this Review, we expect to give new insights into CNTs' toxicological effects at the molecular level and provide new clues for the mitigation of harmful effects emerging from exposure to CNTs.