In any patient who suffers from frequent infections or from a clinical disorder caused by opportunistic organisms, the possibility of an underlying defect in immune defense should be considered. The purpose of this review is to outline a strategic approach towards screening for immunodeficiency in such patients. It should be apparent that the majority of serious immune deficiency states can be detected using a series of relatively simple and readily available investigations. The detection and further definition of other immunodeficiencies may require more sophisticated tests to be performed. The development of new biological tools now permits many of these disorders to be defined at the genetic and molecular level. Finally, early diagnosis of immunodeficiency is important, since it may permit the introduction of corrective measures which can reduce the morbidity and mortality of these disorders.