Anticancer chemotherapies promote a variety of drug-induced cardiotoxicities (DICT), including heart failure, myocardial infarction, arrhythmias, hypertension, and myocarditis. The mechanisms underlying DICT are complex and interconnected often involving multiple on-and-off target effects, making them difficult to predict and manage. Owing to the high myocardial oxygen demand and delicate redox balance, anticancer therapy-induced myocardial oxidative stress is a major mechanism of interest. Novel anticancer therapies such as tyrosine kinase inhibitors (TKIs), monoclonal antibodies (MAbs), 5-fluorouracil (5-FU), and proteasome inhibitors (PIs) have been shown to promote myocardial oxidative stress. With continuous innovation and approval of novel agents, a significant gap has emerged in the recognition, understanding, and treatment of the cardiotoxic effects they may provoke. In this chapter, we (1) describe the mechanisms behind the oxidative stress induced by which TKI, MAbs, 5-FU, and PIs induce oxidative stress in the myocardium; (2) explore myocardial signaling pathways implicated in oxidative damage related to these agents; (3) review pharmacotherapies aimed at mitigating oxidative stress to prevent or treat DICT. With continued improvement in cancer survivorship, there is a growing need for development of pharmacotherapies and prophylaxis which reduce cardiovascular morbidity and mortality secondary to DICT.