Renal cell carcinoma (RCC) accounts for about 3% of all adult malignancies and its incidence is increasing. Smoking, obesity, and end-stage renal disease are important risk factors. Localized RCC may be cured with surgical excision. However, over one-third of patients eventually develop metastatic disease. While chemotherapy and radiation therapy are relatively ineffective for RCC, immunotherapy modestly extends survival and may lead to tumor regression and long-term survival in a small minority of patients. Recently, research into the pathology of genetic syndromes associated with RCC has led to remarkable advances in our understanding of the pathogenesis of sporadic RCC. Rational therapeutic agents developed from this understanding have established new treatment paradigms for this disease.