Metastatic renal cell carcinoma (RCC) has a poor overall survival. Localized RCC remains a surgical disease. About 20%-30% patients who present with limited disease at the time of nephrectomy develop metastasis. The median time to relapse after nephrectomy is 15-18 months. The maximum numbers of relapses are within the first 3 years. In metastatic RCC, immunotherapy is effective in a relatively small percentage of patients but is very toxic. In recent years, there has been an improved understanding of the biology of RCC. This has lead to the development of various agents that target ligands at the molecular level. The hypoxia inducible factor-alfa (HIF-α)/ vascular endothelial growth factor (VEGF) pathway and mammalian target of rapamycin (mTOR) signal transduction pathway are targets for some of these novel agents. Recent randomized phase III trials have shown an improved outcome in patients with metastatic disease who received these targeted agents. This review deals with management of advanced and metastatic renal cell cancer with an emphasis on recently developed targeted therapies.