In the era of targeted therapy the anthracyclines, which were discovered almost half-century ago, may appear to be too old to be good. While it is certainly true that the prototypic anthracyclines have been around for many years, there are robust clinical facts to confute that their time is over. These drugs continue to play an undisputed role in the treatment of many forms of cancer, including hematological malignancies and solid tumors. Unfortunately, however, their main side-effect remains: a life-threatening cardiotoxicity which became apparent at the beginning of anthracyclines' clinical use. In addition to this long-standing problem, we are now discovering that new combination therapies often cause a higher than expected incidence of cardiotoxicity, as if the newly designed drugs make the heart more vulnerable to the old one. Altogether, however, an overwhelming amount of clinical evidence suggests that anthracyclines are too good to be old. Yet, they would look much better if they caused less harm to the heart when administered as either single agents or in combination with otherwise promising new drugs.