Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders characterized by marked peripheral blood and tissue eosinophilia resulting in end organ damage. Recent advances in molecular biology and immunology have led to the identification of a number of distinct subtypes of HES with differing epidemiology, pathogenesis, and prognosis. The ability to distinguish between these HES subtypes combined with the availability of new treatment modalities, including tyrosine kinase inhibitors and monoclonal antibodies, that target specific molecules involved in disease pathogenesis have dramatically altered the approach to the diagnosis and treatment of HES.