Summary: Mepolizumab has been the first monoclonal drug to treat severe eosinophilic asthma since 2015. In 2021, it was approved in the EU for other inflammatory diseases where eosinophils played a key role, such as eosinophilic granulomatosis with polyangiitis (EGPA), idiopathic hypereosinophilic syndrome (HES) and chronic rhinosinusitis with nasal polyps (CRSwNP). The authors hereby demonstrate the efficacy of mepolizumab in clinical trials, real-life studies and personal experience in the therapy of patients with asthma, EGPA, HES and CRSwNP.