Tumor necrosis factor-alpha (TNF-alpha) inhibitors such as adalimumab are increasingly used in the treatment of chronic inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In Europe, this group of drugs also has been approved for therapy of moderate to severe psoriasis recently. With increased application of adalimumab, the possible adverse effects occurring in the course of treatment steadily gained more attention. Among these, infection and localized skin eruptions are the most common. Usually, the cutaneous symptoms rapidly resolve after discontinuation of the drug. Here, however, we report on a woman with rheumatoid arthritis who developed a therapy-refractory, generalized pustular rash during treatment with adalimumab. After different unsuccessful therapeutic attempts, only a combined treatment with prednisone, methotrexate, and cyclosporinee eventually led to marked improvement. To the best of our knowledge, this is the first report on a generalized, therapy-resistant pustulosis as an adverse effect of adalimumab.