Locally advanced and metastatic esophageal cancers have limited treatment options. Esophageal cancer is a very aggressive disease often with bad outcome, and its 5-year survival estimate is under 20%. This dreadful outcome of esophageal cancer is due to its elevated counteraction to chemotherapies. Therefore, new therapeutic approaches are urgently needed to treat esophageal cancer patients to improve clinical outcomes. Immunotherapy is a novel therapeutic approach against several types of cancer including esophageal cancer. Immune checkpoint inhibitor (Pembrolizumab, Nivolumab, and Ipilimumab) immunotherapies have been accepted for the medication of esophageal cancer with potentially significant improvement of outcome in selected patients. Immune checkpoint inhibitors block immune checkpoint ligands like programmed death-ligand 1 or PD-L1 binding with their corresponding parent receptors like programmed cell death protein 1 or PD-1. PD-L1 is expressed on esophageal cancer cells, and it is used as a foretelling biomarker for the curative capability of immune checkpoint interceptors. Microsatellite instability (MSI) results from impaired DNA mismatch repair proteins, and MSI is used to predict the response to immunotherapies in a subset of esophageal cancer. In this review article, we explored the molecular mechanism and emerging roles of immunotherapy in esophageal cancer, and we suggested forthcoming directions for the appropriate implementation of the evolution in immunobiology.