Desmoid tumors, also known as aggressive fibromatosis, are rare fibroblastic tumors that exhibit a wide range of local aggressiveness, from largely indolent to locally destructive. Understanding of the pathogenesis and the great heterogeneity in the natural history of desmoid tumors is invaluable to the development of therapeutic strategies. The optimal treatment protocol has not yet been established and, in many cases, a multidisciplinary approach including surgery, chemotherapy, and radiation therapy has been employed. The rarity of cases in even major tumor centers has traditionally limited the ability to study this disease. Several novel pharmacologic and biologic treatment approaches are actively being developed, although long-term follow-up is needed for their substantiation.