This chapter discusses immunologic aspects of rhinosinusitis, where environmental and host factors including allergy, anatomic abnormalities, and immunodeficiency contribute to the severity of sinusitis. Primary immunodeficiencies (PIDs) are a group of diseases in which there is an intrinsic defect in the host immune system. The typical clinical presentation of antibody deficiencies includes recurrent sinopulmonary infections, chronic gastrointestinal infections, bacteremia, and meningitis. Secondary causes of hypogammaglobulinemia include malignancy, nephrotic syndrome, protein losing enteropathy, and medications. Autoimmune and lymphoproliferative complications may be treated with steroids and other immunosuppressive medications. Among individuals with intact immune function, sinusitis presents similarly to the general population with the characteristic symptoms of nasal congestion, purulent nasal discharge, headache, and facial pain. Iatrogenic causes include immunosuppressive medications following transplant or for the treatment of autoimmune disease, chemotherapeutic agents for hematologic malignancies, biologic agents with immunomodulatory properties, and medications associated with secondary hypogammaglobulinemia.