Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition characterized by type 2 (T2) immune responses with significant impacts on quality of life and health care costs. Local IgE production in nasal polyp tissue plays a key role in the T2 inflammatory cascade. Omalizumab, an anti-IgE monoclonal antibody, is an effective treatment for some patients with CRSwNP regardless of the patient's allergic status. Clinical trials, including the pivotal POLYP 1 and POLYP 2 studies, demonstrated omalizumab's efficacy in reducing nasal polyp size, improving symptom scores, and enhancing quality of life, particularly in patients with comorbid asthma and aspirin-exacerbated respiratory disease. As we summarize in this review, omalizumab's effect appears to involve the reduction in local IgE and T2 inflammation; however, this remains poorly understood. Notably, omalizumab's effectiveness appears to be partially sustained after long-term therapy, though symptoms and inflammation begin to return at discontinuation. Ongoing research is needed to determine the optimal duration of therapy and potential for biologics to modify the disease course. Additionally, further studies are needed to identify biomarkers to predict treatment response and to compare omalizumab with other biologics such as dupilumab in head-to-head trials. Omalizumab is one of the key T2-targeted therapeutic options for CRSwNP, with sustained effectiveness and strong safety profile.