<b><i>Background:</i></b> Allergen immunotherapy (AIT) is the only known causative treatment for <i>Alternaria</i> allergy, but the difficulty in standardizing <i>Alternaria</i> extracts hampers its effectiveness and safety. <b><i>Summary:</i></b> <i>Alternaria</i>, a potent airborne allergen, has a high sensitization rate and is known to trigger the onset and exacerbation of respiratory allergies, even inducing fungal food allergy syndrome in some cases. It can trigger a type 2 inflammatory response, leading to an increase in the secretion of type 2 inflammatory cytokines and eosinophils, which are the culprits behind allergic symptoms. Diagnosing <i>Alternaria</i> allergy is a multistep process, involving a careful examination of clinical symptoms, medical history, skin prick tests, serum-specific IgE detection, or provocation tests. <i>Alt a1</i>, the major component of <i>Alternaria</i>, is a vital player in diagnosing <i>Alternaria</i> allergy through component-resolved diagnosis. Interestingly, <i>Alternaria</i> can reduce the protein activity of other allergens like pollen and cat dander when mixed with them. In order to solve the problems of standardization, efficacy and safety of traditional <i>Alternaria</i> AIT, novel AIT methods targeting <i>Alt a1</i> and innovative vaccines such as epitope, DNA, and mRNA vaccines seem promising in bypassing the standardization issue of <i>Alternaria</i> extracts. But these studies are in early stages, and most researches are still focused on animal models, calling for more evidence to validate their use in humans. <b><i>Key Messages:</i></b> This review delves into the various aspects of <i>Alternaria</i> allergy, including characteristics, epidemiology, immune mechanisms, diagnosis, clinical manifestations, and the application and limitations of <i>Alternaria</i> AIT, aiming to provide a foundation for the management of patients with <i>Alternaria</i> allergy.
