HER2-positive gastric cancer (GC), a unique molecular subtype, has garnered significant interest in recent years. Here, we review clinical trial data on advanced HER2-positive GC from the past 15 years. Trastuzumab plus standard chemotherapy remain the first-line treatment. The initial survival benefits conferred by immune checkpoint inhibitors plus trastuzumab and standard chemotherapy are encouraging. The combination of ramucirumab and mono-chemotherapy, as well as the antibody conjugated drug trastuzumab deruxtecan, is the recommended second-line regimen. Treatment with immune checkpoint inhibitors plus ramucirumab and mono-chemotherapy shows promise. Despite the limited treatment options for third line and beyond, development of novel therapeutic strategies is expected. Although clinical cure of advanced HER2-positive GC is unlikely, current clinical studies offer valuable insight into regimens that prolong survival.