Abstract: The addition of HER2-targeted therapy has markedly improved the survival and prognosis of patients with advanced gastric cancer. Inhibiting the HER2 signaling pathway has become the backbone treatment for advanced HER2-positive gastric cancer in the first-line setting. TOGA trial established trastuzumab in combination with cisplatin and 5-flurouracil as the standard first-line treatment. In the post-TOGA era, combinations of trastuzumab with other chemotherapy agents were proven to be effective as both the second-line treatment and the conversion treatment. Such combinations are promising in the neoadjuvant treatment for locally advanced gastric cancer. Research focuses on the development of novel anti-HER2 agents in combination with agents targeting against other signal pathways. Real-time monitoring of the gene expression profile is the key to discovering the mechanism of trastuzumab resistance. The preliminary results of existing clinical trials have shown potential to overcome resistance to trastuzumab. In this review, we summarized the treatment advancement for HER2 positive gastric cancer and the direction for future development, thereby providing guidance on clinical practice.