Gastric cancer remains a major global malignancy with fewer encouraging treatment despite decades of dedicated research. Targeted cancer therapies bring us the new hope although these new treatment choices have showed only marginal effectiveness over the current treatments. Contemporary research has revealed many pathways related to tumor angiogenesis and proliferation, providing numerous new potential targets. The majority of existing targeting agents are focusing on both EGF/VEGF and their receptors. Bevacizumab is one of the agents targeting to VEGF/VEGFR signal pathway. Based on the AVAGAST trial, bevacizumab demonstrated a negative OS prolongation. Several other compounds, e.g. sorafenib, sunitinib, and everolimus, have also been studied to attempt to develop effective and safe treatments for gastric cancer. However, the results were not promising. A possible reason is the lack of predictive biomarkers for patient selection. For the Her receptor family pathway, Trastuzumab was proved its activity in the HER-2 positive GC patients. Cetuximab, an Her-1(EGFR) inhibitor, is also the potential agent for the treatment of gastric cancer because of a low mutation rate of K-RAS. Further trials are already underway to test potential targeting agents focusing on the downstream components of EGFR, such as inhibitors of mTOR, c-MET, and AKT. The clinical analysis of biomarkers may lead to a better understanding of GC outcomes and appropriate treatment selection.