The ability to make treatment recommendations for patients with gastrointestinal lymphoma is hampered by a lack of prospective trials and by a lack of uniformity in classification and staging. Patients with gastric diffuse large B-cell lymphoma have traditionally been treated with surgery and many physicians continue to recommend this approach. However, recent data suggest that these patients can be treated with combination chemotherapy regimens in the same manner as patients with nodal presentations of diffuse large B-cell lymphoma. There is evidence to suggest that adjuvant radiotherapy may improve the outcome for these patients. The recognition that extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue is a distinct clinicopathologic entity and the elucidation of the pathogenic role of Helicobacter pylori has revolutionized the treatment of these gastric lymphomas. Patients with localized disease should be managed with antibiotic therapy initially. Radiation therapy is extremely effective for these patients, but it should probably be reserved for patients who fail anti-H. pylori treatment.