Approximately 30–40% of patients with renal cell carcinoma present with locally advanced or metastatic disease. With improved response rates and tolerability of targeted agents, the concept of primary targeted therapy followed by consolidative surgery has emerged as a potential paradigm for management of select patients with locally advanced RCC. This strategy may help facilitate less morbid resection of high risk surgical disease and improve outcomes of nephron-sparing surgery for bulky or locally extensive tumors. Herein, we discuss patient selection criteria, assess the emerging data for this approach, and highlight perioperative patient safety concerns, arguments for and against utilization of primary systemic targeted therapy, and future directions for investigation.