Determining the appropriate patients for cytoreductive nephrectomy (CN) has evolved with the integration of more effective systemic therapies for patients with metastatic renal cell carcinoma (mRCC). While previously considered to be first-line therapy for mRCC, CN has not demonstrated a significant survival advantage over systemic therapy in more recent randomized trials when compared with targeted therapy. Conversely, multiple observational studies demonstrate a therapeutic benefit for CN. This review synthesizes the current literature regarding patient selection for CN and further evaluates the role of CN in the current era of immune checkpoint inhibitor therapy. With careful patient selection, CN maintains an important role in the management of mRCC patients.