Most patients who develop kidney cancer are effectively treated with a radical nephrectomy; however, for those patients who present with or develop metastatic disease, the therapeutic options are limited. Interferon and interleukin-2 remain the standard therapies. Several studies have identified the optimal doses and schedules of these cytokines and groups of patients most likely to benefit from immunotherapy. Although cytotoxic chemotherapy continues to have a minor role in patients with clear cell renal carcinoma, it may become the treatment of choice for some patients with variant renal cancers. Novel agents targeting the vascular endothelial growth factor, its receptor, and other hypoxia-induced proteins are showing great promise and soon may expand the therapeutic options for patients with advanced kidney cancer.