The evaluation of response to treatment is a critical step for determining the effectiveness of oncology drugs. Targeted therapies such as tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors are active drugs in patients with metastatic renal cell carcinoma (mRCC). However, treatment with this type of drugs may not result in significant reductions in tumor size, so standard evaluation criteria based on tumor size, such as Response Evaluation Criteria in Solid Tumors (RECIST), may be inappropriate for evaluating response to treatment in patients with mRCC. In fact, targeted therapies apparently yield low response rates that do not reflect increased disease control they may cause and, consequently, the benefit in terms of time to progression. To improve the clinical and radiological evaluation of response to treatment in patients with mRCC treated with targeted drugs, a group of 32 experts in this field have reviewed different aspects related to this issue and have put together a series of recommendations with the intention of providing guidance to clinicians on this matter.