Gastric cancer is a heterogeneous and prevalent disease. The traditional environmental exposures associated with elevated risk of gastric cancer are less prevalent in the USA today. Genetic risks and risks associated with inflammation remain. Most cases are sporadic, and familial clustering is observed in about 10% of the cases. Hereditary gastric cancer accounts for a very low percentage of cases. Here we review the genetic and environmental risk factors associated with the disease. In addition, we will review screening guidelines and current modalities that are available for screening in high-risk populations.