Targeted immunotherapy is founded on the principle that augmentation of effector T cell activity in the tumor microenvironment can translate to tumor regression. Targeted checkpoint inhibitors in the form of agonist or antagonist monoclonal antibodies have come to the fore as a promising strategy to activate systemic immunity and enhance T cell activity by blocking negative signals, enhancing positive signals, or altering the cytokine milieu. This review will examine several immune checkpoints and checkpoint modulators that play a role in cancer pathogenesis, with an emphasis on malignant gliomas.