Adult-onset Still's disease, a febrile, multisystem rheumatic disease, has variable outcomes. Some patients experience remission after a single or multiple inflammatory episodes, while others progress to a chronic course with substantial joint destruction. Although no controlled clinical trials with immunosuppressive agents in this disease have been reported, a number of small uncontrolled studies and case reports describe the use of methotrexate therapy. Methotrexate has shown efficacy for the control of systemic and articular symptoms and its favourable safety profile appears similar to that seen in other rheumatic diseases, when for this indication. The combination of methotrexate and corticosteroids has, over the years, become the first step in the standard of care in adult-onset Still's disease. If the response to this treatment is incomplete, additional therapies, such as biologic agents may be appropriate.