INTRODUCTION: Clinical experience with anti-interleukin (IL)-5 biologic therapies for severe asthma has been increasing, alongside deeper and broader research focusing on the role of IL-5 and the IL-5 targeted mepolizumab. This review aims to provide an update of the evidence on the role of IL-5 and mepolizumab, with discussions of the benefits of mepolizumab and its future potential, to promote the comprehension of the pathophysiology and therapeutic approaches to asthma. AREAS COVERED: For this narrative review, we conducted a database search in PubMed and Embase using the keywords 'IL-5' and 'mepolizumab,' focusing on randomized controlled trials and real-world studies up to September 2024. An overview of the pathogenesis of severe asthma, new insights on the role of IL-5 and mepolizumab, and the evidence on the efficacy and safety of mepolizumab in the treatment of severe eosinophilic asthma is provided, and its benefits in clinical remission and future applications are also discussed. EXPERT OPINION: Mepolizumab holds considerable promise in asthma treatment due to its mechanism of action and multiple potential benefits. In clinical practice, it may be worth considering the exploratory initiation of mepolizumab add-on treatment from the time of medium-dose inhaled glucocorticosteroid use.