Cardiotoxicity represents serious side effects of cancer therapy that affect quality of life and overall survival of patients significantly. Its most severe manifestation, heart failure, has a 5-year survival rate of 50%, worse than that of many types of cancer. However, medications aimed at ameliorating cardiotoxic side-effects of the antineoplastic treatment likely compromise efficacy of it. In this chapter, we propose repositioning inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase, which are used for the treatment of cancers with defective homologous recombination DNA repair, for reducing cardiotoxicity of cancer therapy. We introduce the forms of cardiotoxicity, the involved mechanisms and the therapeutic agents, which cause them. We also present cellular effects of poly(ADP-ribose) polymerase and review the mechanisms involved in antineoplastic and cardioprotective effects of its inhibitors, respectively. Finally, we discuss the risks and benefits of the proposed repositioning.