Esophageal adenocarcinoma is increasing in incidence and arises in a background of reflux induced inflammation, metaplasia, and dysplasia. The proinflammatory transcription factor nuclear factor-kappa B (NF-kappaB) has a central role in inflammation and tumorigenesis. Because a role for NF-kappaB has been implicated in the pathogenesis of esophageal cancer, this transcription factor has been the focus of the current research of this devastating disease. NF-kappaB blocks apoptosis, mediates tumor cell proliferation, and induces resistance to chemotherapeutic drugs. Research efforts to improve the effect of chemotherapy have led to an improvement in patient survival but there is still a need for improvement, and NF-kappaB is a potential target for cancer drug development. In this review, we have attempted to highlight the possible role of NF-kappaB in esophageal adenocarcinoma and discuss the anticancer strategy with NF-kappaB as a promising molecular target in esophageal cancer therapy.