: Trifluridine/tipiracil is a novel oral cytotoxic chemotherapy consisting of a thymidine-based nucleoside analog, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil. Trifluridine/tipiracil was approved for the treatment of metastatic colorectal cancer refractory to standard therapies. A phase II trial in Japan demonstrated that this therapy has antitumor activity and is tolerated by patients with advanced gastric cancer (AGC); as a result, the phase III TAGS trial (Trifluridine/Tipiracil Versus Placebo in Patients With Heavily Pretreated Metastatic Gastric Cancer) was initiated.: Trifluridine/tipiracil has proved effective for heavily pretreated AGC and has thus been approved for use in the United States in February, 2019, Japan in August, 2019 and the European Union in September, 2019. Detail of the phase III TAGS trial are discussed in this review.: Trifluridine/tipiracil after at least two previous courses of systemic chemotherapy improved rates of survival of gastric cancer; thus it has become one of treatment options in affected patients. Currently, several clinical trials of trifluridine/tipiracil in combination with other anticancer agents such as ramucirumab (an anti-vascular endothelial growth factor receptor 2 monoclonal antibody) for patients with AGC are ongoing.