Anthracyclines belong to the most successful antineoplastic drugs, but they are cardiotoxic, which may result in congestive heart failure (CHF). The CHF risk increases with the cumulative anthracycline dose, but it seems also to be modified by individual factors. A role of the individual genetic background is consistent with the altered sensitivity to anthracyclines observed in many transgenic and knockout mouse strains. First clinical data obtained in humans suggest the existence of predisposing variants in genes involved in the oxidative stress, and in the metabolism and transport of anthracyclines. These data will have to be verified in further clinical trials before any attempts of their application in the individual cardiotoxicity prediction can be undertaken. In the meantime, anthracycline-induced cardiotoxicity can be best reduced by application of liposomal anthracycline formulations or by a co-medication with the cardioprotective iron chelator dexrazoxane.