Renal cell carcinoma (RCC) is the most prevalent malignancy within the kidney, and over 40% of patients with RCC will die from their disease. Approximately a third of patients present with metastatic disease and a third of patients undergoing nephrectomy for clinically localized RCC will develop metastases. Metastatic RCC poses a therapeutic challenge due to its resistance to conventional modes of therapy such as chemotherapy and radiation therapy. While it is clear that strides have been made against metastatic RCC, the overall objective response rates of interleukin-2- and interferon-alpha-based immunotherapy remain at approximately 20%. Despite advances in biologic- and immune-based therapies, long-term survival for patients with metastatic RCC remains modest. Furthermore, the toxicity profile of these cytokine regimens is significant. Advances in the understanding of the nature of tumor antigens and their optimal presentation, and in the regulatory mechanisms that govern the immune system, have provided multiple novel immunotherapy intervention strategies with increased specificity and potentially fewer side effects. Such strategies are currently being tested in clinical trials.