Crohn's disease (CD) results from a pathological immune response to luminal antigens in genetically predisposed individuals. Since the causes of CD are complex and only partially understood, treatment is based on the empiric use of anti-inflammatory drugs. Although multiple therapies for CD currently exist, a substantial proportion of patients are unresponsive to conventional agents. Approximately a third of patients fail treatment with TNF antagonists, and up to 40% of patients who initially benefit subsequently lose response. Accordingly, new approaches are required. Ustekinumab, a fully human IgG1-κ monoclonal antibody to the p40 subunit shared by IL-12 and IL-23, has emerged as a promising new treatment for both psoriasis and CD. This article reviews the available data regarding the mechanism of action, pharmacokinetics, efficacy and safety of ustekinumab in CD.