Atopic dermatitis (AD) is a common disease. Severe AD has a significant effect on quality of life and is difficult to treat. We have previously reported 10 patients treated with azathioprine over a 7-year period, to good effect. We have now treated 37 patients over 18 years, and report our findings. The aim of the study was to review the efficacy and safety of azathioprine as a long-term treatment for severe atopic eczema. Patients who began treatment between 1987 and 2005 were identified. The dose and number of courses of azathioprine, duration of treatment, treatment response, and adverse events were recorded up to June 2006. In total, 37 patients were treated with azathioprine. Of these, 15 (40.5%) achieved remission in a median period of 5 months (range 4–29). Nine patients had an initial good response but either did not have sufficient clearance to be able to stop azathioprine, or deteriorated while on treatment over a period of 4–27 months; these were considered late failures. One patient showed no response, and five experienced reactions leading to withdrawal of the drug. Our experience with azathioprine for the treatment of severe atopic eczema, is very encouraging.