Gastric cancer is one of the deadliest and most diagnosed cancers, although the annual incidence has been steadily decreasing. Gastric cancer risk is multifactorial with a clear association with Helicobacter pylori infection. In the United States, the age-adjusted annual incidence is 4.1 per 100,000 people with a mortality rate of 1.6; the global adjusted annual incidence is roughly twice as much with a mortality rate four times higher. No randomized controlled trials have demonstrated the benefit of endoscopy or serum pepsinogen measurement in screening for gastric cancer. Patients are often asymptomatic or have general symptoms such as weight loss, abdominal pain, nausea, and anorexia, which can preclude an early diagnosis. When gastric cancer is suspected, the recommended initial test is upper gastrointestinal endoscopy with multiple tissue biopsies. A multidisciplinary treatment team should be assembled, and shared decision-making should occur with consideration of cancer staging, comorbidities, and available treatments. Treatment is guided by extent of disease, histopathology, and tumor biomarkers. Chemotherapy and radiation, in addition to various targeted therapies, may be treatment options for tumors regardless of resectability. Prognosis is directly related to the extent of disease at diagnosis; the 5-year survival rate of treated localized disease is more than 70% vs less than 10% for distant metastatic disease.