This chapter discusses anti-inflammatory therapy for rhinosinusitis, where therapies directed at reducing sinus inflammation include corticosteroids, antihistamines, leukotriene modifiers and antimicrobials with anti-inflammatory properties. Hydrocortisone is naturally produced human glucocorticoid that plays an important role in metabolic, cardiovascular, immunologic, and homeostatic function. Glucocorticoids are a type of corticosteroid hormone that binds the glucocorticoid receptor and possesses anti-inflammatory properties. Oral steroids are recommended for perioperative use in patients with polyps, with multiple studies showing surgical benefits including shorter operative times, improved visibility and improved postoperative appearance, but no significant reduction in blood loss. Multiple studies evaluated the use of oral steroids as an adjunct to surgical treatment. Cushingoid changes include truncal obesity, moon facies, and dorsocervical fat pad known as buffalo hump. Patients using corticosteroid therapy are more likely to complain of peptic ulcer like symptoms. Biologic activity analysis revealed a significant decrease in blood eosinophil counts in the treatment groups.