Until recently, patients with advanced, unresectable or metastatic renal cell cancer (RCC) had very few therapeutic options. Cytokine therapy, consisting mainly of interferon-alpha and interleukin-2, was considered the mainstay of therapy. A better understanding of the biology of RCC has led to the development of novel therapeutic agents that target angiogenesis. Inactivation of the von Hippel-Lindau tumour-suppressor gene VHL, which is present in the vast majority of clear-cell RCC tumours, leads to overexpression of the vascular endothelial growth factor, which in turn promotes angiogenesis. Recent observations from a number of positive studies with agents such as sunitinib malate, sorafenib, temsirolimus and bevacizumab have led to a rapid and exciting change in the standard of care for patients with advanced renal cell carcinoma. This article reviews these agents in the context of their use in clinical practice and provides suggestions about the appropriateness of various agents in specific clinical situations.