The immune response is a tightly regulated process, which normally results in protection from infection and tolerance of innocuous environmental antigens. However, in allergic disease, the activated immune response results in a chronic pro-inflammatory state characterized by antibody secretion (IgE) and T cell activation to normally well-tolerated antigens. Currently, the treatment of allergic disease is focused on the suppression of key inflammatory mediators or inflammatory cell populations and include anti-histamines, anti-leukotrienes, β2 adrenergic receptor agonists and corticosteroids. However, these approaches only provide a temporary suppression of disease symptoms. Successful long-term treatment can only be provided by allergen-specific immunotherapy (allergen-SIT), which restores normal immunity against allergens. This review will discuss novel approaches to the management of allergy and asthma by targeting the T regulatory cell via modulation of the commensal microbiota and allergen-SIT.