Esophageal cancer is the sixth most common cause of cancer-related death. Esophageal carcinoma can be divided in squamous cell carcinoma and adenocarcinoma by histopathology, and these two main histologic types of esophageal cancer are quite different in many aspects. Apoptosis in esophageal cancer has been extensively studied, and a recognized mechanism for the development of esophageal cancer is an imbalance between cell renewal and cell death, with apoptosis being inhibited. The inability of esophageal cancer to undergo apoptosis when presented with an insult is an important indicator of the propensity for the esophageal malignant transformation. Many of the molecular events necessary for activation, amplification and execution of the apoptotic process in esophageal cancer, and it is evident that diverse drugs can kill esophageal tumor cells through activating common apoptotic pathways. In the last decade, it has been demonstrated that resistance to apoptotic stimuli is a hallmark feature of esophageal cancer and a complex network of pro- and anti-apoptotic proteins that governs the tight regulation along apoptotic pathways in regards of esophageal carcinogenesis and chemotherapy is revealed, and these findings could lead to the identification of several new molecular targets for chemoprevention and chemotherapy in esophageal cancer.