Although recent advances have been made, surgery still remains the mainstay of any curative treatment for gastric cancer patients, with radical gastrectomy representing the procedure of choice. However, patients with locally advanced disease show high rates of locoregional or distant recurrence even after potentially curative resections. According to global results presented in the setting of locally advanced resectable gastric carcinoma, perioperative chemotherapy may be considered a valuable option. On the other hand, clinical trials for advanced gastric cancer seem to suggest that a limit in efficacy has been reached for standard chemotherapy. Interesting data are expected from the development of targeted agents that, similarly to other cancer sites, showed appealing results in gastric cancer as well. Along with new effective therapeutic opportunities, better clinical and molecularly driven patient selection will represent the cornerstone of the global care for these patients.