Rhinosinusitis is among the most common and clinically significant manifestations of primary immunodeficiencies (PIDs), particularly humoral deficiencies, which account for approximately half of all PIDs. Patients with antibody deficiencies are especially prone to recurrent and treatment-resistant rhinosinusitis, whose chronic course often delays the diagnosis of the underlying immune disorder. The aim of this paper is to review current knowledge on the epidemiology, pathophysiology, diagnosis, and treatment of rhinosinusitis in the course of PIDs. The prevalence of immunoglobulin deficiencies is significantly higher in patients with recurrent (13%) and difficult-to-treat (23%) chronic rhinosinusitis (CRS) than in the general population, justifying immunological evaluation in these groups, in line with the EPOS 2020 and ICAR-RS 2021 guidelines. The pathogenesis is multifactorial and involves epithelial barrier dysfunction, impaired opsonization and phagocytosis of encapsulated bacteria, disturbances of innate immunity, and the role of bacterial biofilms. The most important humoral deficiencies associated with rhinosinusitis are discussed: common variable immunodeficiency (CVID), selective IgA deficiency, specific antibody deficiency (SAD), IgG subclass deficiency, X-linked agammaglobulinemia, hyper-IgM syndrome, and activated PI3K delta syndrome. The mainstay of specific treatment remains immunoglobulin replacement therapy in eligible patients, reducing the frequency and severity of infections. Treatment is complemented by targeted antibiotic therapy, antibiotic prophylaxis, vaccination, and – in refractory cases – endoscopic sinus surgery. Early diagnosis of the immune deficiency, prevention of irreversible pulmonary complications, and multidisciplinary collaboration among otolaryngologists, immunologists, and pulmonologists are of key importance.