There is substantial evidence that eosinophils play a major role in the inflammation that characterizes eosinophilic asthma. IL-5 is essential for the maturation and release of eosinophils from the bone marrow, as well as their subsequent accumulation, activation, and persistence in tissues. As a result, IL-5 is an appealing target for preventing or reducing eosinophil-mediated inflammation, leading to the creation of humanized anti-IL-5 monoclonal antibodies such as mepolizumab. This review provides an update on the data supporting the efficacy of mepolizumab therapy for asthma patients. Although early clinical trials with mepolizumab in asthma patients had poor results, it is becoming clear that meaningful therapeutic benefits with this biologic are more likely in carefully chosen patient populations that account for the eosinophilic asthma phenotype. A number of recent trials have found that mepolizumab has a substantial effect on reducing exacerbations as well as a significant glucocorticoid-sparing effect. In carefully chosen groups of asthma patients, mepolizumab is a potentially significant and well-tolerated treatment.