Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug‐induced toxicities. In this paper, we examine the nature of ROS‐induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug‐related side effects including doxorubicin‐induced cardiac damage, azidothymidine‐induced myopathy, and cisplatin‐induced ototoxicity.