The traditional treatments for esophageal squamous cell carcinoma include surgery and radiation as local therapies, then chemotherapy and targeted therapy as systemic treatments. These treatments, either alone or in combination, however, are not satisfactory because of limited efficacy and unfavorable toxicity, calling for new therapeutic strategies. In recent years, immunotherapy, a new weapon in the arsenal against cancer, has shown substantial clinical benefits in patients with esophageal squamous cell carcinoma, particularly ones with locally advanced or metastatic disease. Importantly, accumulating evidence suggests that traditional radiation therapy functions as a powerful adjuvant for immunotherapy by contributing to systemic antitumor immunity, resulting in reduced recurrence risk and improved survival of patients. Here the authors summarize the emerging data on immunotherapy- and radiation therapy-based treatment of esophageal squamous cell carcinoma and discuss the pros and cons of different combinations, aiming at a comprehensive understanding of the proper rationale for the design of effective therapeutic regimens.