Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequent exacerbations despite treatment with high-dose steroid and other currently available therapies. These patients are also at risk of developing steroid-related side effects, and their severe, unrelenting symptoms have a huge impact on health care resources due to frequent hospital admissions and requirement for intensive medication use. Consequently, a compelling need exists for more effective and safer pharmacotherapies to help them achieve adequate disease control. Recent novel therapies for severe asthma are now emerging, some of the most promising of which are monoclonal antibodies. Monoclonal antibodies represent a form of immunotherapy used in a wide variety of therapeutic roles. The spectrum of disease states in which monoclonal antibodies have been approved for therapeutic use now includes respiratory and allergic diseases. At present, only one drug is licensed for allergic asthmatics with severe disease, omalizumab. We review some of the currently available biologics that are approved or under investigation for use in severe asthma. Some have shown to be useful in specifically targeted subpopulations of patients with severe asthma, whereas other have proven to be unsafe and/or unsuccessful. Despite these developments, more effort should be devoted to identifying new molecular targets, testing innovative approaches, and establishing the best use of what is available. Regarding this latter point, identifying individual characteristics that predict successful responses to these treatments is highly desirable.