Peripheral eosinophilia was first associated with systemic disease by Hardy and Anderson in 1968 (Hardy WR, Anderson RE. Ann Intern Med 68(6):1220–1229, 1968. https://doi.org/10.7326/0003-4819-68-6-1220 ). However, a formal definition of hypereosinophilic syndrome (HES) including persistent eosinophilia of greater than 1.5 × 109/L for greater than six months without allergies, parasitic infection, or other causes of eosinophilia and signs or symptoms of organ infiltration was only first described by Chusid and colleagues in 1975 (Chusid MJ, Dale DC, West BC, Wolff SM. Medicine (Baltimore) 54(1):1–27, 1975). Although this definition includes a wide range of disorders, the Working Conference on Eosinophilic Disorders distinguished hypereosinophilia (HE) from hypereosinophilic syndrome (HES) by the presence of organ damage or dysfunction in the latter (Valent P, Klion AD, Horny HP et al. J Allergy Clin Immunol 130(3):607–612 e9, 2012. https://doi.org/10.1016/j.jaci.2012.02.019 ). HES consists of a broad spectrum of conditions that vary considerably in their clinical spectrum, prognosis and importantly response to therapy. These variants include the myeloproliferative HES and chronic eosinophilic leukemia, the lymphocytic variant of HES, and idiopathic or undefined HES. This complex constellation of disorders must be distinguished from the multiple reactive causes of eosinophilia. It is important to note that even in cases of prolonged reactive eosinophilia, organ damage may still occur. The workup and evaluation of prolonged eosinophilia, both HE and HES, require a logically driven and etiology-based approach as this will affect the treatment recommendations and prognosis.