The optimal medical treatment for advanced gastric cancer is currently the source of debate. Cytotoxic treatment has been shown to prolong survival and provide improved symptom control compared with best supportive care alone, but a global standard has not yet been defined. A literature research was undertaken. Results were evaluated by an international author team. The conclusions of this are presented in this paper. Combination chemotherapy with cisplatin and 5-fluorouracil was the preferred first-line chemotherapy, but oxaliplatin has shown equivalent efficacy to cisplatin. Oral fluoropyrimidines, especially S-1 and capecitabine, can substitute for 5-fluorouracil. Modern doublet regimens are preferred in the majority of patients on the basis of a balanced benefit-to-risk ratio. In selected fit and compliant patients, especially those with a high tumor burden or potential secondary resectability, a third drug may be added because triplet chemotherapy led to higher responses rates and enhanced efficacy. However, docetaxel also adds a significant increase in side effects. Monotherapy and early dose modifications should be considered in elderly and infirm patients. Beyond that, our understanding of gastric cancer tumor biology is increasing. In HER2-positive gastric cancer, the addition of the monoclononal anti-HER2 antibody trastuzumab to cisplatin and fluoropyrimidines has prolonged survival duration. Second-line chemotherapy with single agents has now become a proven treatment option. Alternatively, anti-angiogenic treatment with ramucirumab is on the horizon. In conclusion, combination chemotherapy is regarded as the global standard of care for the first-line treatment of advanced gastric cancer. Molecularly targeted treatments are being explored, preferably in combination with a backbone of chemotherapy doublets.