Treatment of gastric cancer is improved over the past years, but unanswered questions remain regarding the efficacy of systemic treatments in adjuvant, neoadjuvant and metastatic setting. It has not been definitively demonstrated the efficacy of adjuvant chemotherapy, that should not be adopted as a standard approach to localized gastric cancer. On the contrary, compelling evidence in support of perioperative chemotherapy with ECF regimen has been recently provided by the MAGIC trial, although many criticisms have been moved to this study. For metastatic setting, a recent meta-analysis showed a small, but significant survival benefit for combination vs single agent chemotherapy, and the V-325 trial demonstrated the superiority of a docetaxel containing regimen (DCF) over a doublet (CF). Finally, the results of ongoing clinical trials on a number of new molecular-targeted drugs should confirm their role in gastric cancer.