mAbs directed against immunologic molecules have emerged as a new class of drugs for treating patients with various immunologic conditions. However, mAb-based treatments may confer a predisposition to various infections. The authors argue that infections in individuals treated with mAbs directed against molecules of the immune system may display some similarities to those in patients with primary immunodeficiency of the corresponding mAb target. A comprehensive dissection of the tremendously diverse human primary immunodeficiencies and the careful description of their clinical features in different populations living in diverse environments thus represents an original, neglected, but promising approach to assessing the potential risk of infection associated with therapeutic mAbs, or with any therapeutic compound inhibiting a specific immunologic molecule.