Gastric cancer incidence and mortality has fallen dramatically over the last 50 years in many regions, but remains the second most common cancer worldwide. Despite a marked decline in fundic and distal tumors, there is a rising incidence of adenocarcinomas of the gastroesophageal junction and gastric cardia, particularly in Western nations. This may imply that there are in fact two diseases differing from each other in epidemiology, etiology, pathology and clinical expression. While surgical resection remains the cornerstone of gastric cancer treatment, the optimum extent of nodal resection remains controversial, with randomized studies failing to show that the D2 procedure improves survival when compared with D1 dissection. The high rate of recurrence and poor survival following surgery provides a rationale for the early use of adjuvant treatment. Adjuvant chemotherapy or adjuvant radiotherapy, when used alone, do not improve survival following resection. However, the results of the recent Intergroup 0116 study are promising in showing that the combination of 5-fluorouracil (5-FU)-based chemotherapy with radiotherapy significantly prolongs disease-free and overall survival when compared with no adjuvant treatment. In advanced gastric cancer, chemotherapy enhances quality of life and prolongs survival when compared with best supportive care. There is no agreed standard of treatment in this setting. Of the commonly used regimens, epirubicin plus cisplatin and 5-FU (ECF) probably has the strongest claim to this role. However, there is a pressing need for new agents, both cytotoxic and molecularly targeted, to be assessed in both the advanced and adjuvant settings.