Metastatic renal cell carcinoma (mRCC) is tumor resistant to all cytotoxic agents. During the last decade, effective targeted therapies emerged including sunitinib, pazopanib and the combination of bevacizumab with IFN-α. The use of bevacizumab plus IFN-α combination in mRCC is supported by the AVOREN trial. Although the primary end point of the AVOREN trial was overall survival, progression-free survival was used to evaluate efficacy and served as the basis of regulatory submission owing to the advent of targeted agents that probably resulted in the prolongation of overall survival in both experimental and control arms. The doubling of median progression-free survival in the AVOREN trials (from 5.4 to 10.2 months) is remarkably similar compared with the results of Phase III trials with sunitinib and pazopanib. Bevacizumab plus IFN-α is the only combined regimen currently used in mRCC and serves as a comparator in the trials combining bevacizumab with other agents.