Summary: Hypereosinophilic syndrome (HES) is a rare, heterogeneous clinical entity characterized by persistent hypereosinophilia and eosinophil-mediated end-organ damage. Although the mechanisms underlying eosinophil overdrive are diverse and many of them are not yet fully understood, HES pathobiology is closely linked to interleukin-5, the principal cytokine regulating eosinophil proliferation, differentiation, activation, trafficking, and survival. HES is diagnosed by documenting an absolute eosinophil count of at least 1.5 × 10⁹/L on two separate occasions at least two weeks apart, together with evidence of organ dysfunction caused by eosinophilic tissue infiltration, after exclusion of alternative etiologies. Four major forms are recognized: congenital, primary/neoplastic, secondary/reactive, and idiopathic HES. Clinical manifestations are multisystemic and most frequently involve the cardiovascular, respiratory, gastrointestinal, cutaneous, and nervous systems. Diagnostic evaluation requires comprehensive assessment of organ involvement and exclusion of clonal hematologic disorders, particularly those resulting from rearrangements involving genes coding PDGFRA/B (especially with fused gene formation FIP1L1::PDGFRA), FGFR1, and JAK2. Systemic glucocorticosteroids remain first-line therapy, although their long-term administration is limited by adverse effects. Major therapeutic advances have emerged with the introduction of biologics interfering the IL-5-axis. Mepolizumab, first in class, is now available under the National Health Fund (NHF) reimbursement in Poland in steroid resistant/refractory HES.