Omalizumab is a monoclonal anti-IgE antibody that has been used to treat allergic asthma for over a decade. The use of omalizumab to treat other diseases has largely been limited to case reports until the recently reported large multicenter studies that have established omalizumab as an effective treatment option for chronic spontaneous urticaria. The utility of omalizumab to treat nonallergic asthma and allergic rhinitis and the added safety and therapeutic benefits in combination with allergen immunotherapy have been demonstrated in placebo-controlled trials. Data supporting the clinical efficacy of omalizumab in treating atopic dermatitis, physical urticarias, mast cell disorders, food allergy, and various other allergic disorders have shown promise in small clinical trials and case studies. More carefully designed, large clinical trials of high quality are needed to fully appreciate the potential of omalizumab in treating various allergic and nonallergic diseases.