Gastric cancer is a major worldwide problem and is a leading cause of death. The incidence of distal gastric cancer is declining; however, there has been a rapid rise in the incidence of adenocarcinoma of the gastroesophageal junction, which is a more aggressive entity. Combination chemotherapy has significant activity in the treatment of both of these diseases, improving overall survival and quality of life. Despite these improvements, median survival remains at approximately 9 months in patients who are diagnosed at stage IV. This review examines recent advances in the treatment of gastroesophageal junction adenocarcinoma and gastric cancer, newer agents and the potential agents that are in development, which can be logically applied to the treatment of this devastating disease.