Gastric cancer is a global health issue. Most cases are diagnosed at an advanced stage with poor prognosis. Current therapies have a modest impact on survival. Surgery remains the only potentially curative treatment, but is associated with a high rate of locoregional recurrence and distant metastases. Total gastrectomy for proximal cancers is complicated by postoperative morbidity and quality-of-life impairment. Combined-modality therapy may improve outcomes in this disease. Adjuvant therapy for gastric cancer has now become the standard in the Western world. However, adjuvant therapy improves survival by only a few months and is associated with high morbidity. Neoadjuvant therapy is commonly used for esophageal and gastroesophageal junction cancers, but is still regarded as investigational in gastric cancer. Several small phase II studies indicate the feasibility of neoadjuvant strategies. The incorporation of novel, targeted agents into neoadjuvant programs and an assessment of biologic changes within the tumor may refine therapy. This article provides a concise review of the literature on neoadjuvant therapy for gastric cancer and suggests avenues for further investigation.