In patients with metastatic gastric cancer, median overall survival with standard chemotherapy remains under 1 year. As such, effective new treatments with acceptable tolerability are urgently needed. Amplification/overexpression of HER2 is reported in approximately 20% of gastric tumors, providing a rationale to investigate trastuzumab, a monoclonal antibody against HER2, in this setting. In the Phase III international Trastuzumab for Gastric Cancer (ToGA) study, the addition of trastuzumab to chemotherapy significantly improved overall survival without compromising safety in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer. The purpose of this review is to discuss clinical data supporting the role of trastuzumab in metastatic gastric cancer, and consider the optimization of gastric cancer-specific HER2 testing and analysis.