The demographics of esophageal and gastric cancer have been changing dramatically in the United States over the past several decades. While incidence rates for esophageal squamous cell carcinoma and distal gastric carcinoma have been declining, the trends for adenocarcinoma of the esophagus and proximal stomach have been rising rapidly, particularly among white males. The incidence of these upper gastrointestinal (GI) malignancies varies widely based on geographic location, race, and socioeconomic status. The primary causes of squamous cell carcinoma of the esophagus are tobacco use and alcohol consumption, whereas the main risk factors for adenocarcinoma of the esophagus are gastroesophageal reflux disease and obesity. Dietary factors and Helicobacter pylori infection play an important role in the development of gastric cancer. Understanding the epidemiology and etiologies of esophageal and gastric carcinomas will lead to the development of interventions for screening and prevention in high-risk populations.