Doxorubicin (Dox) is frequently used as a frontline chemotherapeutic agent against a variety of cancers. Tremendous progress has been made on its optimal usage over the last 40 years. However, cardiotoxicity still remains a major concern. The great promise in this matter is that the mechanisms leading to antitumor activity appear to be different from those leading to Dox-induced cardiomyopathy. In this regard, various cardioprotective agents have been discussed. Attention should be drawn to probucol, a lipid-lowering agent with potent antioxidant properties, which provides complete protection against Dox-induced cardiomyopathy in rats without interfering with the antitumor properties of Dox in an experimental setting. Clinical trials employing Dox therapy in combination with probucol are needed to determine whether the outstanding findings in animal experiments can be extrapolated to clinical results. We have much further to go before the establishment of cancer therapies without any risk of cardiac side effects.