Hypereosinophilic syndrome (HES) is characterized by hypereosinophilia associated with subsequent damage of one or more target organs. HES has various causes, that can be divided into primary (clonal involvement of the myeloid lineage), secondary (polyclonal by interleukin-5 production), and idiopathic. Thanks to technological advances, particularly in genetics, six clinical-biological variants could be defined, thus leading to the emergence of targeted therapies. Imatinib, a tyrosine kinase inhibitor, is used in myeloproliferative HES (M-HES), while other variants are treated in first line by corticosteroids. The development of new agents, such as IL-5 inhibitors (mepolizumab), has allowed sparing corticosteroids and thus avoiding their adverse effects, thereby improving the patients’ quality of life.