Mast cells have been mainly regarded as effector cells in IgE-dependent mucosal immunity, including the host response to helminthic parasites but also the formidable and sometimes fatal anaphylactic reactions to inhaled or ingested allergens. Work performed mostly within the last decade revealed novel functions for mast cells as critical initiators of fast inflammatory reactions upon IgE-independent activation. Thus, their role as a sentinel in innate immunity also suggests that mast cells are able to bridge innate and adaptive immunity. Herein, we will summarize the accumulating evidence that mast cells are also able to promote and to modulate the development of adaptive immune reactions with emphasis on their role in allergic sensitization in skin and lung. Based on murine data published so far, it is becoming apparent that mast cells and their mediators are of critical relevance for allergen sensitization under conditions which more closely resemble physiological contact with allergens. Yet, the function of mast cells can sometimes be bypassed using vigorous sensitization protocols, a finding which should be taken into account when animal models for complex human diseases are investigated.