Children frequently present with a history of repeated infections. When these infections are serious and respond poorly to normally successful treatment programs, suspicion of a basic defect in one or more host defense mechanisms may be raised. In such cases defects in humoral or cell-mediated immunity, phagocytic cell functions or the complement system must be sought. Much of our knowledge about the development and functions of these cooperating but independent systems allows clinical observations to provide a generally accurate prediction of the nature of the defect involved. The degree of sophistication with which the systems can be evaluated and the possibilities for therapeutic manipulation are rapidly increasing. In this article are outlined the basic pathophysiological mechanisms needed to approach these increasingly recognized problems.