In this review, the normal immune system, primary and secondary immunodeficiency diseases, and nonimmunologic causes of recurrent infection have been described. With this information, any child with frequent infections can be evaluated in a sound and logical fashion. The history and physical examination are usually sufficient to rule out a significant immunodeficiency. For those in whom that is not the case, screening laboratory tests, most of which are readily available in hospitals and commercial laboratories, can and should be performed by the primary caretaker. These serve conclusively to rule in or rule out an immunodeficiency disorder in most patients and to establish the need for referral to an immunologist in the rare patient. With a few notable exceptions, the prognosis for children with immunodeficiency diseases has improved dramatically in the past two decades. This progress, fortunately, is certain to continue as the intricacies of the immune system and its genetic basis are gradually unraveled. However, the success of these new technologies depends on the ability of the primary pediatrician to identify these patients early, before permanent structural damage has occurred or a life-threatening viral infection been acquired.