Historically, treatment for renal cell carcinoma (RCC) has included the immune therapies interleukin-2 (IL-2) and interferon alpha (IFN-α). In recent years, “targeted” therapies which block VEGF or mTOR pathways have become the standard of care and have replaced immune therapy for front-line treatment of metastatic RCC. While these targeted therapies have been shown to prolong survival, many come with significant toxicities and responses are temporary. The durable response seen in patients treated with IL-2 provide proof of concept that immunotherapy has the potential for lasting clinical benefit in a subset of RCC patients. However, low response rates and significant toxicity limit the widespread use of IL-2. Newer immune therapies have the potential to offer durable responses without the side effect profile of conventional cytokine-based immunotherapy. These therapies target important regulatory pathways of the immune system, so-called “checkpoints” and include cytotoxic T lymphocyte antigen 4 (CTLA-4), Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PDL-1).