The transmural inflammation characteristic of Crohn's disease predisposes patients to the formation of fistulas. Up to 50% of patients with Crohn's disease are affected by fistulas, which is a major problem given the considerable morbidity associated with this complication. Appropriate treatment of fistulas requires knowledge of specific pharmacological and surgical therapies. Treatment options depend on the severity of symptoms, fistula location, the number and complexity of fistula tracts, and the presence of rectal complications. Internal fistulas, such as ileoileal or ileocecal fistulas, are mostly asymptomatic and do not require intervention. By contrast, perianal fistulas can be painful and abscesses may develop that require surgical drainage with or without seton placement, transient ileostomy, or in severe cases, proctectomy. This Review describes the epidemiology and pathology of fistulizing Crohn's disease. Particular focus is given to external and perianal fistulas, for which treatment options are well established. Available therapeutic options, including novel therapies, are discussed. Wherever possible, practical and evidence-based treatment regimens for Crohn's disease-associated fistulas are provided.