While the widespread use of imaging has resulted in an increasing number of incidentally detected renal cancers, up to one third of patients present with metastatic disease and a significant number of those with clinically localized disease subsequently develop metastasis. The prognosis for patients with metastatic disease has traditionally been poor, with a 2-year survival of only 10 to 20%. However, over the past decade a number of developments have enhanced the treatment of these patients. Phase III trials have demonstrated a significant improvement in overall survival for well-selected patients undergoing cytoreductive nephrectomy prior to immunotherapy. Meanwhile, the recent introduction of molecular targeted agents has resulted in improved response rates and tolerability compared with immunotherapy, and has prompted a re-evaluation of the role and timing of surgery in patients with advanced disease. This review examines the role of surgical therapy for patients with metastatic disease in the new era of molecular targeted therapy.