In this Practice Point commentary, we discuss the findings and limitations of a randomized, placebo-controlled trial conducted by Lewis and colleagues that examined the efficacy of rosiglitazone for the treatment of patients with mild-to-moderately active ulcerative colitis. The results show that rosiglitazone had superior efficacy to placebo for inducing clinical response and remission. However, the efficacy of rosiglitazone in this setting was modest. We believe that this finding might be attributable to the high numbers of patients included in the trial who were refractory to conventional therapy. Rosiglitazone might be more effective if combined with 5-aminosalicylic acid therapy and used in patients with less-refractory disease. We highlight the issues to consider when interpreting and generalizing these findings to clinical practice.