The molecular bases of approximately one hundred primary immune deficiencies (PID) have been identified over the last 15 years. In adults, the diagnosis of PID cannot be evoked before ruling out acquired immunodeficiencies, which are far more frequent. The search for specific PIDs may be oriented by the type of agent responsible for severe and/or recurrent infection. More rarely, other clinical manifestations such as granulomatosis, autoimmune manifestations, hemophagocytic syndrome, lymphoproliferation, or solid tumors may also lead to the identification of PID.