Severe persistent asthma causes a substantial morbidity and mortality burden and is frequently inadequately controlled despite intensive guideline-based therapy. Targeting allergic inflammatory processes that underlie the pathogenesis of severe persistent asthma improves asthma control in a significant proportion of patients. Omalizumab, a humanized monoclonal anti-immunoglobulin E (IgE) antibody, has been developed to target IgE, which is central to triggering and maintaining allergic airway inflammation. In a comprehensive program of clinical trials, omalizumab has been shown to reduce asthma exacerbation and emergency visit rates, and to improve quality of life in patients with severe persistent allergic asthma. It is difficult to predict which patients would most benefit from omalizumab treatment; accurate selection and dosing of patients are essential to achieve benefit. Patients need to have convincing IgE-mediated asthma and be dosed according to pre-treatment serum total IgE level and body weight, using a specified dosing table. Based on clinical trial data analysis, it is recommended that treatment response is evaluated by the physician after 16 weeks of therapy. Treatment should only be continued in responders, i.e. those judged by the physician to have achieved a marked improvement or complete asthma control. Omalizumab is generally well tolerated. Anaphylactic-like reactions are rare (0.1% of patients) and less common than encountered with other biologics.