Mast cells (MCs) have primarily been associated with mediating the pathological secondary responses to allergens in sensitized hosts. In view of the recent evidence for a MC role in modulating primary immune responses to pathogens, the likelihood for a role of MCs in influencing primary immune response to allergens has grown. New evidence suggests that MCs drive the development of Th2 responses to allergens, particularly when allergen exposure occurs concomitantly with exposure to pathogen products present in the environment. These new roles for MCs in allergy and infection suggest additional drug targets to prevent the development of allergic disease and allergic exacerbations of established disease.