Most primary immunodeficiencies are diagnosed in children and, therefore, are managed by pediatricians and pediatric specialists. Generally, internists and adult gastroenterologists only rarely encounter patients with primary immunodeficiency, and have little or no involvement in actual treatment. However, gastroenterologists should be familiar with primary immunodeficiency because 1) current and future therapy for immunodeficiency will allow more patients to survive into adulthood, 2) some primary immunodeficiencies, particularly common variable immunodeficiency, may have their first clinical manifestation in adolescence or early adulthood, and 3) recently it has been hypothesized that Crohn's disease may be an immunodeficiency. Detailed treatment recommendations are not included in this review, as subspecialists in pediatrics, immunology, and hematology manage such treatments. Of far greater importance, even in this treatment-oriented forum, is the enhancement of our awareness of these disorders.