Cardiotoxicity induced by anticancer drugs interferes with the continuation of optimal treatment, inducing life-threatening risks or leading to long-term morbidity. The heart is a complex pluricellular organ comprised of cardiomyocytes and non-cardiomyocytes. Although the study of these cell populations has been often focusing on cardiomyocytes, the contributions of non-cardiomyocytes to development and disease are increasingly being appreciated as both dynamic and essential. This review summarized the role of non-cardiomyocytes in anticancer drug-induced cardiotoxicity, including the mechanism of direct damage to resident non-cardiomyocytes, cardiomyocytes injury caused by paracrine modality, myocardial inflammation induced by transient cell populations and the protective agents that focused on non-cardiomyocytes.