Esophageal cancer remains an important public health problem worldwide. Understanding and preventing the occurrence of this cancer are complicated by the fact that the 2 major histologic types, squamous cell carcinoma (SCC) and adenocarcinoma (ACE), differ substantially in their underlying patterns of incidence and key etiologic factors. The main characteristic that they share is a high mortality rate. Surveillance, Epidemiology, and End Results data for the United States show a 30% drop in incidence of SCC between 1973 and 2002, with declines greatest in black males, although incidence in this group remains high compared with other groups. Incidence of ACE has increased 4-fold over the same period, with a nearly 5-fold increase in white males. Alcohol and smoking are major, established risk factors for SCC. Gastroesophageal reflux disease is consistently associated with increased risk of ACE, whereas infection with Helicobacter pylori may reduce its incidence. Increasing body mass index is also strongly associated with ACE risk while showing no association or an inverse relationship with SCC. Diet affects both types of esophageal cancer, with a higher intake of fruits and vegetables associated with reduced incidence. Aspirin and other nonsteroidal antiinflammatory drugs are currently the most promising chemoprevention candidates for both cancer types. Lifestyle changes, such as weight loss and exercise, are additional ways in which the incidence of ACE might be reduced.