In Brief Primary immune deficiency diseases (PIDD) are immune disorders that affect approximately 1 in 2000 people in the general population and most often result from genetic defects. Patients with PIDD experience markedly increased susceptibility to recurrent and persistent infections, especially sinopulmonary infections. If untreated, patients experience increased morbidity and mortality and a significantly impaired quality of life. Unfortunately, despite increased awareness of PIDD among health care professionals and the public, a substantial proportion of patients with PIDD remain undiagnosed and untreated. Results from surveys and PIDD registries reveal that less than 50% of eligible patients receive appropriate treatment. In evaluating individuals with frequent or severe sinopulmonary infections, clinicians should consider immunologic problems in the differential diagnoses. For patients with a confirmed diagnosis of PIDD, referral to a specialist such as a pulmonologist or immunologist with expertise in managing patients with PIDD is essential. Immunoglobulin (Ig) replacement therapy is recommended for many types of PIDD. Clinical trials have demonstrated significant reductions in infections and mortality and improvement in quality of life with regular administration of intravenous or subcutaneous Ig. Experimental treatments for specific PIDD conditions include bone marrow transplantation and gene therapy. Increased awareness of the features of PIDD and an understanding of effective treatment are essential to improving the recognition and management of PIDD. Primary immune deficiency diseases (PIDD) are more than 100 inherited immune system disorders that leave patients susceptible to severe, recurrent, and persistent infections. Many clinical features of PIDD resemble symptoms of more common infectious diseases such as sinusitis, otitis, bronchitis, or pneumonia, so patients are often undiagnosed or misdiagnosed. Because sinopulmonary infections are common with PIDD, pulmonologists have a critically important position in the accurate diagnosis and effective treatment of patients with PIDD.