Eosinophils are innate immune leukocytes recruited in large numbers to sites of allergic inflammation and parasitic infections. Recent studies show additional pleiotropic effects of recruited eosinophils impacting immunomodulation, tissue homeostasis and repair. Pathologic conditions accompanied by blood eosinophilia are quite frequent in medical practice and may raise serious differential diagnosis problems in severe cases, that require a multidisciplinary approach. Hypereosinophilia may be reactive to other diseases or primary, representing hypereosinophilic syndromes, that are diagnosed based on clinical and laboratory criteria, according to actual international guidelines. The etiopathogenic diagnosis is difficult and delayed in many cases and clinical evolution may be severe, with multiorgan involvement and poor prognosis. Some cases remain idiopathic, despite exhaustive investigation. This paper aims to review the most recent data in the literature referring to the role of eosinophils in human pathology, diagnostic criteria and treatment strategies of hypereosinophilic syndromes, actual classification and to draw some useful recommendations in clinical practice.