Background: Despite recent advances in oncological treatment, gastric and esophageal cancer remain neoplastic diseases with poor prognoses. The only potential curative treatment is surgical resection with adjuvant or neoadjuvant chemotherapy/chemoradiotherapy. Targeted therapy of metastatic disease unfortunately does not provide better outcomes than for other tumor types, with the exception of trastuzumab and ramucirumab, which have relatively limited efficacy. Immunotherapy is a rapidly evolving treatment that has influenced the treatment guidelines for many tumors. In the present review, we summarize clinical trials of checkpoint inhibitors for the treatment of gastric and esophageal cancer, including published results and the perspectives of ongoing trials. Results and Discussion: Gastric and esophageal cancer are tumors with high mutation loads that have attracted considerable attention since the beginning of interest in immunotherapy. Phase I clinical trials (Keynote 012, Javelin, KEYNOTE 028) have demonstrated efficacy and acceptable toxicity. These studies were followed by phase II clinical trials (KEYNOTE 059, CheckMate 032, JapicCTI-No.142422), which showed about a 10–30% overall tumor response rate and confirmed the predictive role of PD-L1 expression. Ongoing phase III clinical trials (CheckMate 648, KEYNOTE 181, KEYNOTE 590, CheckMate 577) should finally confirm whether checkpoint inhibitors have a role to play in a palliative and adjuvant setting. Conclusion: Checkpoint inhibitors are perspective treatment modalities for gastric and esophageal tumors.