Clear-cell renal cell carcinoma (RCC) is the most common kidney cancer. New treatment options of localized RCC recently incorporated include laparoscopic surgery, nephron-sparing surgery, ablative techniques and active surveillance. But 50 % of patients may develop disease recurrence attributable to subclinical metastases. In these cases, and considering the low benefits of chemotherapy, new targeted therapies such as tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors have been developed as first- and second-line treatment. Both sunitinib and pazopanib are TKIs that constitute the first-line treatment option in patients with metastatic RCC. As second-line treatment, sequential therapy with a second TKI or a mTOR inhibitor is recommended. This review has collected together a series of recommendations issued by the Spanish Oncology Genitourinary Group with the aim of facilitating the treatment of these patients. Each recommendation is accompanied by the level of evidence and grade of recommendation on the basis of the available data.