The natural history of Crohn's disease is characterized by recurrent exacerbations. A small, but significant, number of pediatric patients with Crohn's disease are resistant to standard medical therapies. The goal of therapy in pediatric patients is not only to achieve and maintain clinical remission, but also to promote growth, development and improve quality of life. All of this needs to be achieved within a relatively short window of opportunity, before growth and development deficiencies become permanent. The standard therapy for pediatric patients with Crohn's disease consists of 5-aminosalicylic-acid compounds, antibiotics and enteral nutrition. Enteral nutrition has an excellent adverse-effect profile and, in addition to its therapeutic effect, positively impacts growth and nutritional status. Immunomodulating medications, such as azathioprine, 6-mercaptopurine and methotrexate, are frequently used to maintain remission, and to treat corticosteroid-dependent and perianal disease. Recently, biologic treatment with the anti-tumor-necrosis-factor-alpha antibody infliximab has dramatically changed the therapeutic approach. The long-term safety of this therapy still needs to be established. Limited data are available on other biologic therapies, which, at this point in time, are considered experimental and are only available through clinical trials.