Immunotherapy results in a small overall survival advantage in metastatic renal cell carcinoma (RCC), but there is a need to develop more effective systemic therapies. Angiogenesis has an important role in the pathophysiology of RCC and vascular endothelial growth factor (VEGF) is a key mediator of this process. Sorafenib (BAY 43-9006) is a new agent belonging to a class of drugs called kinase inhibitors and inhibits the VEGF, platelet-derived growth factor (PDGF), and c-KIT receptor tyrosine kinases, amongst others. Sorafenib has shown significant activity with manageable toxicity in metastatic RCC in phase 2 studies in patients pretreated with immunotherapy, whilst prolonged progression-free survival in comparison with placebo in a phase 3 study has been reported. Further phase 3 trials in advanced disease are ongoing and a trial of adjuvant sorafenib therapy in RCC is planned.