**Abstract**

Eosinophilic airway inflammation is a hallmark in the pathophysiological and clinical definition of asthma. In the last decades, asthma evolved in the recognition of different phenotypes identified by natural history, clinical and physiological characteristics, and the underlying immune mechanisms. Among these phenotypes, many have been associated with eosinophilic-driven inflammation. This is the case of either early-onset allergic Th2 asthma or late-onset persistent eosinophilic asthma. Both animal models and analysis from human samples have contributed to elucidate the role of eosinophils in the asthmatic inflammatory response and the synergic role of Th2 cytokines. In severe asthma, high numbers of eosinophils can persist despite treatment with inhaled and oral corticosteroids leading to the definition of severe refractory eosinophilic asthma. The combined role of IL-4-, IL-13- and IL-5-associated pathways has focused the view over the T2-type endotypes, wherein a specific biological pathway explains the observable properties of different phenotypes and the identifiable biomarkers can predict response to monoclonal antibodies directed against a selected immune target. In the era of precision medicine and personalized therapy, both the identification of Th2 molecules and eosinophils as targets and biomarkers have become the best clue for treating and monitoring severe asthma.

**Keywords:** severe asthma, eosinophilic phenotypes, T2-type inflammation, eosinophilic refractory asthma, anti-IL5 treatment
