Currently, the management of localized renal cell carcinoma (RCC) is surgical. Unfortunately, many cases of high-risk RCC recur following resection and develop metastatic disease, an event that usually results in death. Because previous attempts to improve survival with adjuvant therapy have been unsuccessful, the US Food and Drug Administration's approval of three new agents for metastatic RCC has generated renewed interest in evaluating agents in the adjuvant setting for high-risk RCC. This article discusses the rationale for the use of these and other novel agents and reviews currently ongoing adjuvant trials as well as considerations for the development of new trials for adjuvant therapies.