Adults presenting with recurrent infections require an approach that allows exclusion of underlying immunodeficiency. While secondary causes of immunodeficiency are the most common, primary immunodeficiency disease (PID) may present for the first time in adults. Failure to consider this diagnosis in adults and children leads to a major diagnostic delay. Recurrent localised infections generally suggest an underlying anatomical rather than an immune defect. PIDs that are most commonly encountered include common variable immunodeficiency, immunoglobulin (Ig) A deficiency, and IgG subclass deficiency. I suggest a diagnostic approach with relevant immune tests, depending on the clinical picture. The essential role of vaccination with polysaccharide and protein antigens to evaluate B-cell functional capacity, is highlighted. Principles of management are provided, including indications for immunoglobulin replacement therapy.