Gastric cancer is a global health problem; although incidence rates are declining, it remains the third most common cause of cancer death worldwide. Patients with advanced disease have limited treatment options, and most will live for less than 2 years. Therefore, exploration of gastric cancer disease biology is warranted to identify new targets for treatment. Recent comprehensive molecular analyses have identified distinct subgroups of gastric cancer that may have therapeutic relevance. With the exception of microsatellite-unstable tumors, however, the potential for genomically guided therapy has not been realized.