Renal cell carcinoma (RCC), the most common form of kidney cancer, accounts for 3% of all adult malignancies and its incidence has significantly increased over the last 20 years. RCC claims 13,000 lives annually in the USA and more than 100,000 worldwide. A better understanding of the molecular basis of RCC has facilitated the development of novel and more selective therapeutic approaches. An important role in RCC oncogenesis is played by the receptor for HGF, Met, which has attracted considerable attention, more recently as a molecular target for cancer therapy, and several drugs selectively targeting this pathway are now in clinical trials. This review will focus on efforts to understand the role of the Met signaling pathway in renal cancer and how this has contributed to the development of potent and selective drug candidates.