The child who has recurrent infections poses one of the most difficult diagnostic challenges in pediatrics. The clinician faces a two-fold challenge in determining first whether the child is normal or has a serious disease, and then, in the latter case, how to confirm or exclude the diagnosis with the minimum number of the least invasive tests. It is hoped that, in the absence of good-quality evidence for most clinical scenarios, the experience-based approach described in this article may prove a useful guide to the clinician.