Gastric cancer is one of the leading causes of cancer death worldwide. Because of its heterogeneity, gastric cancer has been an interesting model for studying carcinogenesis and tumorigenesis. Various genetic and molecular alterations are found in gastric cancer that underlie the malignant transformation of gastric mucosa during the multistep process of gastric cancer pathogenesis. Although the detailed mechanisms of gastric cancer development remain uncertain, the enhancement in understanding of its molecular biology in recent years has led to a better perspective on the molecular epidemiology, carcinogenesis, and pathogenesis of gastric cancer. More importantly, it is becoming possible to use molecular markers in differential diagnosis, prognostic evaluation, and specific clinical interventions. Because multiple molecular alterations are frequently noted in gastric cancer and because its histology is complex, new technologies for studying its molecular biology are important to further evaluate gastric carcinogenesis. This review describes our current knowledge of the molecular basis of gastric cancer as it relates to molecular epidemiology, multiple molecular alterations in pathogenesis, and molecular determinants of invasion and metastasis, as well as their potential clinical applications.