Gastric cancer is one of the major malignancies in the world. This article summarizes the current understanding of the worldwide burden of this disease, its geographic variation, and temporal trends. An overview is presented of known risk factors, including genetic, dietary, and behavioral, but focuses on Helicobacter pylori infection as the most important factor in noncardia gastric cancer. When the data and the literature allow, we distinguish between cardia and noncardia sub-sites, as it is now clear that these two anatomic locations present distinct and sometimes opposite epidemiological characteristics. Copyright © 2013 Elsevier Inc. All rights reserved.