During the past half-decade, clinical trials have permitted major progress in treatment of metastatic renal cell carcinoma with the first generation of targeted therapies (bevacizumab, sunitinib, sorafenib, everolimus, and temsirolimus). New targeted agents such as axitinib, tivozanib, and dovitinib, all of which are tyrosine kinase inhibitors, have been developed in treatment of metastatic renal cell carcinoma. In the same time, more information regarding mechanism of disease and drug resistance shed light on new targets and new potent agents. We report an overview of the more relevant data published over the past year, which may modify the therapeutic landscape of kidney cancer in the near future.