Gastric cancer is a major clinical challenge, with poor overall prognosis and limited life expectancy for patients with advanced disease. Even with surgery and other modalities, palliation is often difficult. Improvement of response rates has evolved with the development of standard regimens and those incorporating newer chemotherapy agents, such as oral fluoropyrimidines, the taxanes, camptothecins, novel platinums (eg, oxaliplatin [Eloxatin]), and antifolates (eg, pemetrexed [Alimta]). Ongoing trials with these regimens aim toward improving survival, as well as improving the safety profile. It is hoped that in conjunction with molecular research in the pathogenesis of gastric cancer and development of targeted therapies in this disease, these trial data might lead to the evolution of treatment strategies that could prove effective.