Hypereosinophilic syndrome (HES) is a rare disorder that is characterized by 
persistent and marked eosinophilia combined with organ system dysfunction. HES 
has substantial clinical heterogeneity but can be fatal without treatment, 
especially in patients who present with a myelodysplastic variant of the 
disorder. Although the pathophysiology of HES is poorly defined, dysregulation 
of cytokines (interleukin 5 [IL-5], IL-3, granulocyte-macrophage 
colony-stimulating factor [GM-CSF]) responsible for the maturation of 
eosinophils is a primary feature. Of these cytokines, IL-5 appears to have the 
greatest role in the regulation of eosinophil maturation. There is no Food and 
Drug Administration-approved treatment for HES as yet; current strategies are 
designed to lower blood eosinophils and attempt to limit end-organ damage. 
Historically, corticosteroids and cytotoxic agents have been the mainstays of 
therapy, with biological response modifiers such as interferon-alpha also 
effective in some patients. However, despite improvements in survival, available 
agents have significant limitations in terms of efficacy, tolerability, and 
long-term toxicity. More recently, new agents directed at specific targets in 
the pathogenesis of HES have been developed. These include imatinib mesylate, a 
tyrosine kinase inhibitor, and more recently, mepolizumab, an anti-IL-5 
monoclonal antibody. In a small case series of patients, these agents have been 
shown to produce hematological and clinical responses in patients with HES, 
although they may be effective in different subsets of patients. These targeted 
therapies have the potential to improve clinical outcomes and to further the 
understanding the pathophysiology of this difficult-to-treat condition.