Although radical surgical R0 resections are the basis of cure for gastric cancer, surgery alone only provides long-term survival in 20-30% of patients with advanced-stage disease. Thus, in Western and European countries, advanced gastric cancer has a high risk of recurrence and metachronous metastases. Very recently, multimodal strategies combining different neoadjuvant and/or adjuvant protocols have improved the prognosis of gastric cancer when combined with surgery with curative intent. As used in palliative regimens, the combination of cisplatin with intravenous or oral fluoropyrimidines has been the integral component of such (neo)adjuvant strategies. However, the cytotoxic agents docetaxel, oxaliplatin and irinotecan and new targeted biologicals such as cetuximab, bevacizumab or panitumumab are currently under investigation, with or without irradiation, in multimodal treatment regimens. These studies may further increase R0 resection rates, and prolong disease-free and overall survival times in the treatment of advanced gastric cancer. This article reviews the most relevant literature on multimodal treatment of gastric cancer, and discusses future strategies to improve locoregional failures.