While eradication of Helicobacter pylori leads to durable remissions in up to 75 % of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma and therefore, has been well established as first-line therapy of choice, there is no standard of care for relapsed, refractory or extragastric MALT lymphoma. Both in gastric as well as extragastric MALT lymphoma, local therapy results in high rates of local control, but MALT lymphoma may be disseminated in a significant number of patients, making systemic treatment approaches reasonable. Different classical cytostatic agents have successfully been tested in the past. However, MALT lymphoma usually runs an indolent clinical course and thus, recent trials have focussed on chemotherapeutics with a favourable toxicity profile, e.g. chlorambucil or bendamustine with or without rituximab (R), and new immunomodulatory drugs, e.g. lenalidomide. Results are promising and further, and especially more mature data with a longer follow-up are awaited. In addition, efforts have been made to characterise the activity of antibiotic therapy in extragastric MALT lymphoma, particularly in the setting of ocular adnexal manifestations. Doxycyclin-treatment achieved response rates of 45–65 % in several series, which was independent of the presence of a Chlamydophila psittaci infection. Furthermore, the macrolide antibiotic clarithromycin has become a matter of interest for the treatment of ocular adnexal MALT lymphoma as this substance exerts not only antibiotic, but also direct anti-tumor and immunomodulatory effects. In view of recent data, this short review focuses on highlights and recent results of systemic and antimicrobial therapy in MALT lymphoma.