Despite a decline in the incidence in Western countries, gastric cancer is still the second most common cause of cancer-related death worldwide. Many advances have been made in diagnosis and treatment of gastric cancer in the last decades but the prognosis for gastric cancer patients remains disappointing, especially in more advanced stages. The poor outcome associated with surgical resection with curative intent has generated intensive investigation of combined modality treatment approaches including systemic chemotherapy and radiotherapy to prevent recurrences and improve survival. In this setting the use of perioperative chemotherapy or postoperative chemoradiotherapy has demonstrated to give survival benefits. In advanced disease, major improvements of the last years are represented by the introduction of oral fluoropyrimidines and drugs such as docetaxel or irinotecan and the demonstration of efficacy of the anti-HER2 agent trastuzumab.