Esophagogastric cancers are aggressive malignancies, with poor prognosis despite current standard-of-care therapies. PD-1 inhibitors are a newer class of antitumor agents with the potential to improve outcomes among appropriately selected patients. This review provides an overview of the key trials that have guided the use of PD-1 and PD-L1 inhibitors in the refractory and first-line settings. We highlight recent studies investigating the role of genomic classification in predicting therapeutic activity of PD-1 inhibitors. In addition, there is a discussion of the use of different scoring systems and criteria to determine PD-L1 positivity, the impact on the therapeutic use of immune checkpoint inhibition with anti-PD-1 agents, and the controversies in current methods of PD-L1 testing and their implications in patient selection for anti-PD-1 therapy.