Allergen-specific immunotherapy (AIT) has been used clinically for over 100 years as a treatment for allergic rhinitis (AR). Meta analysis has shown that AIT is effective in reducing symptoms in adults and children for both AR and asthma in sensitised patients. This presentation will review mechanisms of action for AIT considering new technologies in practice; subcutaneous and sublingual allergen immunotherapy, and in development; synthetic peptide immunoregulatory epitopes, recombinant native, hypoallergenic and hybrid allergy vaccines. The focus will be on grass pollen (GP), the major outdoor aeroallergen source globally. Whilst currently available standardized allergen immunotherapy is available for temperate GP, allergens of subtropical (Panicoideae and Chloridoideae) and temperate (Pooideae) species differ by over 30% of their primary sequence and show incomplete serum IgE cross-reactivity. In the Grass Pollen Allergy Survey we observed regional variations in allergic sensitivity to temperate and subtropical GP in Queensland, Sydney, Perth and Adelaide, which extended findings of earlier studies in Melbourne. Patients with GP allergy showed regional differences in levels and patterns of allergic sensitivity with subtropical or temperate GP consistent with the biogeographical distribution of the grasses. The outcomes provide insights for design of more specific diagnosis and treatment of GP allergy. The utility of using molecular component resolved diagnosis in determining levels and patterns of specific IgE to GP allergens for identifying those in the community with hayfever who are at greater risk of severe allergic airway inflammation and asthma exacerbation during thunderstorm asthma events and seasonally high GP exposure is considered.