Drug-Induced Ototoxicity is a widespread global problem occurring as a side effect of otherwise effective therapies for conditions such as bacterial sepsis (aminoglycosides) and cancers (platinum-based chemotherapy). It is becoming clear that having the conditions requiring these drugs itself puts the patient at increased risk for acquiring life-long hearing loss. This apparent clinical paradox places the provider in difficult position where treating the life-threatening condition will most likely result in poor hearing outcomes. Since these ototoxic therapies are both life-saving and economically viable, understanding the mechanisms of hearing loss and developing effective strategies to preserve hearing during treatment for life-threatening illness has the potential to greatly enhance the quality of life in vulnerable patient populations.