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To discuss the advanced practice nurse’s diagnosis and management of an unsuspected primary immunodeficiency (PI) disease, X-linked agammaglobulinemia (XLA), in a child.Review of historical and current scientific literature, practice guidelines, and a case study.While a diagnosis of XLA is most commonly made in the first 3 years of life, this case study presents a 10-year-old boy’s circuitous route to this diagnosis. A diagnosis of an immune defect should be considered for patients with chronic, recurrent, or unusual infections. For patients who lack immune globulins and antibodies, intravenous immune globulin, given monthly and continued throughout life, is the standard of care.Diagnosis of children and adults with primary immune deficiency diseases may be delayed if practitioners fail to find the root cause of recurrent infections. Nurses as patient advocates should recognize the need for a referral in clinical cases where immunodeficiency may not be suspected. Evaluation of the immune system is performed by a panel of blood tests. There is a need to increase awareness of PI, their manifestations, and treatment among nurses both at the bedside and in advanced practice settings.