There have been tremendous advancements in immunotherapy approaches for patients with renal cell carcinoma (RCC) from the initial interleukin-2 era to the current immune checkpoint inhibitor (ICI) combinations. Several ICI-based therapies have greatly improved outcomes for patients with RCC with the potential for durable responses for a subset of patients. In this chapter, we review the data of key frontline ICI-based combinations for RCC in the metastatic setting and recent data on adjuvant immunotherapy. We also discuss recent data on the role of immunotherapy rechallenge following prior ICI treatment as well as emerging novel immunotherapy strategies with chimeric antigen receptor (CAR) T and gut microbiome interventions. Lastly, we highlight a multidisciplinary team-based approach for patients with RCC treated with ICI including management of immune-related adverse events as well as potential role of cytoreductive nephrectomy in an evolving treatment landscape.