A child with recurrent infections represents a challenge to the pediatrician who must identify, among a large number of repeatedly infected but nevertheless healthy children whose parents need to be reassured, the rare cases of potentially severe immune deficiency. This can be most successfully achieved through the measurement of IgA, IgG, and antibody titers to vaccine (tetanus, diphtheria, Haemophilus influenzae B) and exposure (pneumococcus) antigens. The presence of normal antibody responses makes it possible to rule out underlying immune deficiency in a sensitive and specific manner. Conversely, abnormally weak antibody responses identify the children who have to be referred without delay for further investigation of a potential immune defect. This article indicates for which pediatric patients an immunodeficiency screening should be considered, and how to analyze its results.