Although it is recognized that airway inflammation is key to asthma pathogenesis, the marked heterogeneity in its clinical course and variations in response to treatment make it a challenging condition for the development of novel and effective biologic-based therapies. Biopharmaceutical approaches have identified new therapies that target key cells and mediators that drive inflammatory responses in the asthmatic lung. Such an approach resulted in the development of biologics targeted at inhibiting IL-4, IL-5 and IL-13. With the notable exception of the anti-IgE monoclonal antibody omalizumab, early clinical trials with cytokine-targeted biologics in patients with asthma were, for the most part, disappointing, despite being highly effective in animal models of asthma. It is becoming apparent that significant clinical effects with anticytokine-based therapies are more likely in carefully selected patient populations that take asthma phenotypes into account. The development of discriminatory biomarkers and genetic profiling may aid identification of such patients with asthma. This review summarizes recent evidence demonstrating the effectiveness or otherwise of monoclonal antibody-based therapies in patients with asthma.