Monoclonal antibodies targeting programmed death 1, programmed death ligand 1, and cytotoxic T-lymphocyte antigen 4 pathways are currently in development for metastatic renal cell carcinoma. By inhibiting these immune regulatory pathways, these agents improve the immune response to cancer with the goal of creating durable responses. Although still early in development, several agents have been studied in phases I and II setting for metastatic renal cell carcinoma, with 1 drug in phase III testing (nivolumab). The unique toxicity profile of this class of therapy presents challenges to the treating clinician. Ongoing clinical trials hope to define patients who will benefit based on predictive biomarkers. Immune checkpoint inhibitors may play a key role in the future of management of solid tumors including kidney cancer.