Anthracyclines are a class of chemotherapeutics commonly used to treat a range of cancers. Despite success in improving cancer survival rates, anthracyclines have dose-limiting cardiotoxicity that prevents more widespread clinical utility. Currently, the therapeutic options for these patients are limited to the iron-chelating agent dexrazoxane, the only FDA-approved drug for anthracycline cardiotoxicity. However, the clinical use of dexrazoxane has failed to replicate expectations from preclinical studies. A limited list of GPCRs have been identified as pathogenic in anthracycline-induced cardiotoxicity, including receptors (frizzled, adrenoreceptors, angiotensin II receptors) previously implicated in cardiac remodeling in other pathologies. The RNA sequencing of iPSC-derived cardiac myocytes from patients has increased our understanding of the pathogenic mechanisms driving cardiotoxicity. These data identified changes in the expression of novel GPCRs, heterotrimeric G proteins, and the regulatory pathways that govern downstream signaling. This review will capitalize on insights from these experiments to explain aspects of disease pathogenesis and cardiac remodeling. These data provide a cornucopia of possible unexplored potential pathways by which we can reduce the cardiotoxic side effects, without compromising the anti-cancer effects, of doxorubicin and provide new therapeutic options to improve the recovery and quality of life for patients undergoing chemotherapy.