Targeted therapies have improved survival in patients with metastatic renal cell cancer (RCC); however, expert opinion on the optimal therapeutic strategy is divided. This retrospective study evaluates different sequential schemes of targeted therapies in 310 patients with advanced/metastatic RCC who received different systemic agents - sorafenib, sunitinib, bevacizumab, everolimus, temsirolimus and axitinib - alone or in different sequences, until disease progression or intolerable toxicity (median follow-up: 37 months). The median overall survival (OS) was 22 months and the 5-year OS was 23.4%; differential therapeutic schemes were not associated with differences in OS. A worse performance status, no nephrectomy and a poor-risk classification according to the Motzer criteria was associated with a shorter OS. These findings support the use of targeted therapies in the treatment of RCC, even in a large unselected population from a single institution, and suggest that treatment should be tailored to meet individual circumstances and needs.