Omalizumab, a humanized monoclonal antibody against IgE, is clinically efficacious when it neutralizes almost all free IgE and reduces IgE receptors on basophils and mast cells. Asthmatic subjects on inhaled corticosteroids who are treated with omalizumab as an add-on therapy experience only modest benefits in symptoms and perhaps in quality of life, but the most significant effects are reductions in airway inflammation and in exacerbation rate. Airway obstruction and hyperresponsiveness do not change significantly. Although the magnitude of the beneficial effects is small, they are observed even in the most severe cases, particularly the reduction in exacerbation rate. The safety profile of omalizumab is very encouraging, although phase IV studies are ongoing to clarify the incidence of neoplasias. Because of its cost, omalizumab therapy may be most cost-effective in patients with severe and refractory asthma, particularly those with frequent exacerbations requiring hospital care. Further clinical studies are now evaluating the best place for omalizumab in the algorithm of asthma management.