Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and antimalarial medications. Because their benefits in combating certain life-threatening diseases often outweigh the risks, the use of these ototoxic drugs cannot simply be avoided. In this review, the authors discuss some of the most frequently used ototoxic drugs and what is currently known about the cell and molecular mechanisms underlying their noxious effects. The authors also provide suggestions for the clinical management of ototoxic medications, including ototoxic detection and drug monitoring. Understanding the mechanisms of drug ototoxicity may lead to new strategies for preventing and curing drug-induced hearing loss, as well as developing new pharmacological drugs with less toxic side effects.