In the past few years, advances in the understanding of the pathogenesis of renal cell carcinoma (RCC) have resulted in the identification of new therapeutic targets, and ultimately, the development of new targeted agents for the treatment of the disease. This paper reviews latest data in RCC for the recently approved agents sunitinib and sorafenib, as well as other molecularly targeted drugs, presented at the annual meeting of the American Society for Clinical Oncology, held in Atlanta, Georgia, in June 2006. Clinical findings to date show that these new agents are challenging the role of cytokines in this setting, and for some (e.g. sunitinib) a substantially improved efficacy profile (progression-free survival and response) over conventional cytokine therapy has been reported. While challenges remain with regard to optimal use of these agents, the outlook for patients with advanced RCC has improved considerably and there is great hope for continuing progress.