Objective To describe the dissemination of targeted therapy and its impact on rates of cytoreductive nephrectomy (CNx) and among privately insured patients with metastatic renal cell carcinoma (mRCC). Patients and Methods All mRCC patients aged <65 years with systemic therapy from 2004 to 2010 (n = 610) were identified from a large private insurance database. Trends in the relative utilization of immunotherapy and targeted therapy, as well as CNx treatment patterns, were compared between early (2004-2007) and late (2008-2010) periods. Multivariate logistic regression analysis identified predictors of CNx, and adjusted predicted probabilities of CNx were compared. Results Among the 610 patients, 535 (87.7%) and 43 (7.1%) patients received targeted or immunotherapy alone, whereas 32 patients (5.2%) received both. A total of 145 patients (23.8%) underwent CNx. From 2004 to 2010, the annual rate of targeted therapy utilization increased markedly (from 10% to 98.2%; P <.001), whereas immunotherapy receipt declined (from 100% to 1.9%; P <.001). Annual CNx utilization peaked at 31.3% in 2005, and declined to 14.8% by 2010 (P =.045). Independent predictors receipt of CNx on multivariate analysis included age >55 years (odds ratio, 0.80; 95% confidence interval, 0.66-0.96; P =.02) and female gender (odds ratio, 0.79; 95% confidence interval, 0.63-0.99; P =.04). Notably, the predicted probability of CNx decreased between the early and late period among patients irrespective of age, gender, targeted therapy, or number of systemic therapies (P <.001 for all). Conclusion During this study period, targeted therapy has largely supplanted the use of immunotherapy among privately insured patients with mRCC treated with systemic therapy, whereas rates of CNx have declined steadily since 2005.