The overall 5-year survival of patients with gastric cancer is only 23% in the US compared with 60% in Japan. For Western patients, detecting the disease earlier and applying treatment quality control could substantially improve clinical outcome. For the treatment of gastric cancer, complete tumor resection, whenever feasible, is the standard treatment. Resection of the primary tumor (partial or total gastrectomy) is based on standardized criteria of the tumor, such as location, stage, histology, and surgical margins. The extent of regional lymphadenectomy required, however, has been a matter of considerable debate. Emerging evidence from the latest randomized controlled trials show that extended (D2) lymphadenectomy is safe and able to cure 20% of patients with N2-disease compared with 0% treated with limited D1 dissection, provided that the optimal surgical technique is used. Estimates suggest that this N2-specific subgroup advantage reflects a potential absolute overall survival benefit of 3-6%. Postoperative decisions about adjuvant chemotherapy and radiotherapy are based on pathologic staging, the extent of surgery performed (D0/D1 vs D2/D3) and the risk-benefit ratio. Recurrence-risk and mortality-risk reduction is achievable with a carefully planned relapse-prevention guided therapeutic strategy. Patient-related factors (tumor features and expected recurrence-risk magnitude) and treatment-related factors (surgical experience, adjuvant treatment risk-benefit ratio) should be considered on an individual basis. In future, genomic-based approaches will help to provide a more personalized therapeutic approach and improve patient outcome.