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Children with a history of recurrent or unusual infections present a diagnostic challenge. Differentiation between frequent infections caused by common risk factors, versus primary immune dysfunction should be based on a detailed history and physical examination and, if indicated, followed by appropriate laboratory studies. A high index of suspicion could lead to an early diagnosis and treatment of an underlying immune deficiency disease. This article presents to physicians an approach to the evaluation of children with recurrent infections. Important details from the history and physical examination, and an appropriate choice of screening laboratory test to be ordered in a given situation are discussed.