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Severe equine asthma is a chronic respiratory disease of adult horses, occurring when genetically susceptible individuals are exposed to environmental aeroallergens. This results in airway inflammation, mucus accumulation and bronchial constriction. Although several studies aimed at evaluating the genetic and immune pathways associated with the disease, the results reported are inconsistent. Furthermore, the complexity and heterogeneity of this disease bears great similarity to what is described for human asthma. Currently available studies identified two chromosome regions (ECA13 and ECA15) and several genes associated with the disease. The inflammatory response appears to be mediated by T helper cells (Th1, Th2, Th17) and neutrophilic inflammation significantly contributes to the persistence of airway inflammatory status. This review evaluates the reported findings pertaining to the genetical and immunological background of severe equine asthma and reflects on their implications in the pathophysiology of the disease whilst discussing further areas of research interest aiming at advancing treatment and prognosis of affected individuals.