Allergic diseases are mediated by IgE and, hence, neutralizing IgE to attenuate type I hypersensitivity reactions may result in clinical benefits. This has been mainly established in several large pre- and postmarketing studies of the humanized monoclonal anti-IgE antibody, omalizumab, in patients with allergic asthma. In this patient population, omalizumab has been shown to have beneficial effects in subjective and objective outcome measures, as well as resulting in reductions in medication use. Omalizumab is now globally licensed for use in severe persistent asthma. However, a growing number of reports suggest that anti-IgE treatment may also be beneficial to patients suffering from other IgE-related conditions, including allergic rhinitis, peanut allergy, latex sensitivity, atopic dermatitis, chronic urticaria and allergic bronchopulmonary aspergillosis. For these patients, and specifically for those with severe refractory disease, anti-IgE treatments might have the potential of reducing their financial burden both in terms of medical costs and of loss of productivity in missed work and school days. In this reveiw, we evaluate the evidence in support of a more extensive role for omalizumab in a number of non-asthma IgE-related conditions, and particularly where intensive treatment has not been effective. However, studies with larger numbers of well-characterized patients will be necessary to provide sound evidence regarding the benefit of IgE blockade in these challenging conditions.