Renal cell carcinomas make up 3% of all cancers and one in four patients is metastatic at time of diagnosis.This cancer is one of the most resistant to cytotoxic chemotherapy. Studies have shown that the efficiency ofinterferon-alpha and/or interleukin-2 based immune therapies is limited in patients with metastatic renal cellcarcinoma but latest advances in molecular biology and genetic science have resulted in better understanding ofits biology. Tumor angiogenesis, tumor proliferation and metastasis develop by the activation of signal messagepathways playing a role in the development of renal cell carcinomas. Better definition of these pathways hascaused an increase in preclinic and clinical studies into target directed treatment of renal cell carcinoma. Manyrecent studies have shown that numerous anti-angiogenic agents have marked clinical activity. In this article, thefocus is on general characteristics of molecular pathways playing a major role in renal cell carcinoma, reviewingclinical information onagents used in the target directed treatment of metastatic lesions.