Several biologic agents have been recently developed and studied as treatment for disseminated clear cell RCC. Tyrosine kinase inhibitors, such as sorafenib and sunitinib, have been found to inhibit tumor growth and angiogenesis by blocking the vascular endothelial growth factor receptor (VEGF-R). Meanwhile, bevacizumab is an monoclonal antibody that has also been shown to be effective, and which acts by directly binding circulating VEGF. Additional agents with proven efficacy include mTOR (mammalian target of rapamycin) inhibitors, such as temsirolimus and everolimus. Finally, high-dose interleukin 2 (IL-2) can activate an immune response against the tumor, with modest response rates. The effect of these various agents on the growth and overall prognosis of non–clear cell tumors is unclear and remains under active investigation.