Crohn disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by a relapsing course and variable presentation that often includes abdominal pain, diarrhea, and fatigue. CD frequently presents during childhood, resulting in pediatric-specific complications, such as growth failure and delayed puberty. Conventional drug therapy for moderate to severe pediatric CD includes induction of remission with corticosteroids, and maintenance of remission with immunomodulators. Patients who have an inadequate response to standard therapy are being increasingly treated with anti-tumor necrosis factor-alpha (TNFalpha) agents. Infliximab has been the most widely studied anti-TNFalpha agent in pediatric CD, and has been shown to be efficacious in this condition. Adalimumab has been proven to be efficacious in adults with CD, but there has been only a single case report in children. CDP571 has been tested in 20 children with CD, showing some efficacy. Finally, thalidomide therapy has been associated with improvement in two small case series. Toxicities of these agents include infusion reactions, infections, malignancies, neurologic disorders, and hematologic derangements.