Therapies currently approved in renal cell carcinoma (RCC) include tyrosine kinase inhibitors, immune checkpoint inhibitors, and inhibitors of mTOR signaling. Increased understanding of the biology of clear cell and non-clear cell RCC has led to development of agents that target hypoxia-inducible factor 2 and MET, while there is ongoing exploration of targeting immune pathways other than the programmed death ligand 1 or cytotoxic T-lymphocyte-associated protein 4 checkpoints.