Because no single predisposing disease can account for the formation of nasal polyps in all patients, medical and surgical therapy has to be directed toward the inflammatory process and/or the underlying infection, together with the development of local tissue pathology. Light and electron microscopical studies in experimental models have revealed that the initial polyp formation sequence involves multiple epithelial disruptions with proliferating granulation tissue, where immature branching epithelium migrates to cover the mucosal defect. Other branches spread into the underlying connective tissue, where intraepithelial microcavities with a differentiated epithelial lining separate the developing polyp body from the adjacent mucosa. Polyp formation and growth is thus activated and perpetuated by an integrated process of mucosal epithelium, matrix, and inflammatory cells, which in turn may be initiated by both infectious and noninfectious inflammation. Glucocorticosteroids display a favorable therapeutic profile, directly preventing both polyp formation and polyp growth, but also by reducing local pathology and inflammatory exudate with bacterial colonization. Steroids often combined with antibiotics or surgery aimed at specific events in polyp development have to be used in relation to disease progression, and severity as well as differences in clinical behavior due to the multifactorial pathophysiological events of nasal polyposis.