Gentamicin and cisplatin are clinically widely used pharmacological agents which may induce irreversible hearing loss as a side effect. Concerning the pathomechanisms of ototoxicity as well as preventive strategies there are similarities but also some differences. In this review we focus on the role of reactive oxygen species, the antioxidant system, cellular iron and calcium as well as nitric oxide and neurotrophins on gentamicin- and cisplatin-ototoxicity. Furthermore we deal with apoptotic and necrotic cell death as well as the role of mitochondria in these cell injury processes.