Chronic sinusitis with nasal polyposis has a detrimental impact on quality of life and may exacerbate coexisting conditions such as asthma. This presentation will outline the latest theories on disease pathogenesis as well as promote rational medical and surgical strategies for severe nasal polyposis management, specifically the two toughest areas of nasal polyposis to treat - Allergic Fungal Sinusitis (AFS) and Asprin-Exacerbated Respiratory Disease (AERD) Treatments designed to decrease reliance on systemic steroids including surgical methods and complementary medical therapeutics such as topical steroid irrigations, macrolides, and anti-leukotrienes will be discussed. We will provide the latest innovations in medical and surgical treatments through a case-based approach of difficult patients and strategies for success illustrating these advancements.