Studies in the early 1980s with anti-idiotype mAbs provided clinical proof that mAbs could be safe and effective antilymphoma agents; however, mAb therapy of lymphoma did not become practical until the chimaeric anti-CD20 mAb rituximab was developed. As a single agent, rituximab is well-tolerated and has clinical efficacy in select patient populations. A number of mechanisms of action have been identified that appear to contribute to the observed antilymphoma effects of mAb. Growing evidence suggests that multiple interacting mechanisms are likely to be involved. Anti-CD20-based radioimmunotherapy and combinations of mAb and chemotherapy are showing promise. mAbs that recognise other target antigens and immunotoxins have been evaluated clinically. It remains unclear whether these other mAbs provide value added beyond rituximab. Research geared towards understanding mAb mechanisms of action and the rational design of the next generation of mAb-based regimens will allow us to take full advantage of this exciting new mode of therapy.