Anthracyclines have substantially improved the prognosis of patients with aggressive lymphoma. Increased risk of cardiotoxicity is a significant concern associated with the use of anthracyclines, particularly in patients with pre-existing heart disease, elderly or very young patients, and those with established risk factors. A prolonged infusional schedule may alleviate the toxicity, but is difficult to implement in clinical practice. The administration of dexrazoxane, a cardioprotective agent, may ameliorate cardiotoxicity associated with anthracyclines. However, it has come under scrutiny because of increased risk of hematological second malignancies particularly in children. Liposomal doxorubicin is a viable alternative with less cardiotoxicity and similar efficacy than conventional doxorubicin. Patients should be screened for heart disease and known risk factors before initiating therapy. Risk factors should be adequately controlled and alternatives should be explored in patients at risk for cardiac toxicity. Survivorship care is an integral part of treatment, and patients should be monitored for late effects of treatment.