Mucosa-associated lymphoid tissue (MALT) lymphoma is amongst the most common lymphoma entities and comprises about 7% of all newly diagnosed NHL. Roughly 50% of all MALT lymphomas are located in the stomach, where a pathophysiological link with Helicobacter pylori (HP) with consecutive response to HP eradication therapy has been established. In view of this, HP eradication has become the standard approach to patients with localised disease and signs of HP infection. Recent data, however, have suggested that also HP-negative patients might benefit from antibiotic treatment. On the other hand, an unexpectedly high rate of autoimmune diseases, e.g. Hashimoto’s thyroiditis or Sjogren’s syndrome has been found in gastric MALT lymphoma, and such patients do not respond to HP eradication in the large majority. In case of non-response to antibiotics the standard approach in such patients is currently not clear. Both radiation as well as chemotherapy has shown promising results, and currently there is only one randomised study, which nevertheless suggests superiority of chemotherapy in terms of event-free survival at 10 years. The optimal chemotherapeutic regimen, however, has not been established yet, although various agents and combinations have demonstrated high activity, albeit in small trials. In view of this, patients with gastric MALT lymphoma unresponsive to antibiotics should be included in clinical trials.