Allergens are mostly innocuous antigens that elicit powerful T helper cell type 2 (Th2) responses leading to hyper-immunoglobulin E (IgE) production and allergy. Research carried out over several years has highlighted the possible role of the inherent protease activity, surface features and glycosylation patterns of allergens in the engagement of a Th2 signalling pathway. It is thought that allergens possess common features and patterns that enable them to be recognized by innate immune defences as Th2-inducing antigens. These events are further amplified by proteolytically active allergens through digestion of cell surface molecules involved in regulating innate and adaptive immune functions, favouring Th2 responses. A greater understanding of the molecular features that make proteins allergenic will help define new therapeutic targets aimed at blocking allergen recognition and protease activity.