Diagnosis of renal cell carcinoma (RCC) frequently occurs at advanced stages, severely limiting the success of treatment, and median survival is barely more than a year. Previously, treatment of renal cancer was limited to nephrectomy or immunotherapy (interleukin or interferon-α), which was effective in a small subset of patients but often was accompanied by severe side effects. New orally administered targeted therapies have become available, offering broader benefits to patients with advanced RCC. Sorafenib is an oral, multikinase inhibitor recently approved by the U.S. Food and Drug Administration as treatment for advanced RCC based on its extension of median progression-free survival from 12-24 weeks. Oncology nurses must ensure patient adherence and manage side effects of emerging treatments. This article reviews the management of skin rash, hand-foot skin reaction, hypertension, diarrhea, and fatigue in patients receiving sorafenib. In addition, a case study of a patient receiving sorafenib is presented.