The incidence of esophageal adenocarcinoma is increasing largely in Western populations, and patients diagnosed with this cancer continue to have a poor prognosis. The major risk factors are gastroesophageal reflux disease and Barrett's esophagus, both of which are associated with inflammation of the esophageal squamous epithelium, a condition called reflux esophagitis. The cellular mechanisms contributing to cancer development in the esophagus are poorly understood. The chronic inflammation that is present in Barrett's esophagus creates an environment suitable for DNA damage and altered expression of genes involved in cellular proliferation and inhibition of apoptosis. Key players in the inflammatory cascade include generation of free radicals, activation of kinases pathways and transcription factors, and production of cytokines and inflammatory enzymes. The current review highlights the link between reflux-induced inflammation and esophageal carcinogenesis. Understanding the molecular pathways involved in inflammation-associated esophageal tumorigenesis could enable the development of targeted therapies and offer a better therapeutic treatment in esophageal cancer.