The prognosis of locally advanced gastric cancer remains poor. It has been shown that multimodal treatment can improve the outcome in comparison to surgery alone. Two randomized studies that have been performed in Europe have shown that peri-operative chemotherapy significantly improves the survival of patients with adenocarcinoma of the stomach and of the gastro-esophageal junction. These results have a profound effect on the treatment of patients presenting with stage II or stage III disease. For more than 10 years it has been accepted that responding patients have a significantly improved prognosis compared to non-responding patients. Therefore, (early) response evaluation or response prediction is of utmost importance. After neoadjuvant chemotherapy patients should undergo a D-2 lymphadenectomy due to the high probability of lymph node metastasis. Neither mortality nor complication rate are increased after neoadjuvant chemotherapy for gastric cancer. Patients with locally advanced gastric cancer should always be referred to experienced high volume centers, where the findings are discussed in a multidisciplinary tumor board.