Cardiotoxicity is an emerging concern with a new class of drugs known as targeted agents, which include trastuzumab and sunitinib. Sunitinib is a small molecule that inhibits multiple tyrosine kinase receptors. This drug was approved by the United States Food and Drug Administration in 2006 for the treatment of clear cell metastatic renal cell carcinoma and advanced gastrointestinal stromal tumors. We describe a 65-year-old woman who was treated with sunitinib for metastatic clear cell renal cell carcinoma. After 5 months of therapy, she developed acute heart failure requiring hospitalization; sunitinib was immediately discontinued. The patient had classic symptoms of heart failure, including pleural effusion. An echocardiogram revealed a left ventricular ejection fraction of 30%. She received standard treatment for heart failure, including a beta-blocker, an angiotensin-converting enzyme inhibitor, and diuretics. Within 1 month, the patient's symptoms resolved, and subsequent cardiac evaluation showed that her left ventricular ejection fraction returned to normal. According to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute, her cardiac event associated with sunitinib was defined as grade III toxicity. One month later, sorafenib, another tyrosine kinase inhibitor, was started with the aim of continuing her previous response to sunitinib. After 7 months of sorafenib therapy, the patient had no evidence of heart failure, and her condition was responding to treatment. Clinicians should be aware that sunitinib-induced heart failure occurs occultly and that many--but not all--cases resolve with discontinuation of the drug. Use of sorafenib after sunitinib-induced heart failure appears to be safe and effective, which suggests that cardiotoxicity is not a general class effect of the tyrosine kinase inhibitors.