Increasing knowledge of how cancer cells escape immune destruction has significantly driven the evolution of cancer immunotherapy. In particular, studies describing how different immune checkpoints, including the PD-1 and CTLA-4 pathways, function to attenuate T cell antitumor activity have revealed novel opportunities for therapeutic intervention. Researchers have made promising strides in inhibiting these checkpoints to unleash the T cells’ tumor-killing potential. Given that both radiotherapy and chemotherapy can also mobilize antitumor T cells, there is great excitement that checkpoint inhibition and other immunomodulatory approaches can be combined with conventional modalities to maximize clinical outcomes for a number of malignancies.