Mast cells (MCs) are Multifunctional cells that are well recognized with their functions in allergic diseases and certain types of parasitic infections. However, their essential contribution to other aspects of host defence and immune regulation has only recently begun to be widely accepted. Until recently, MCs have been considered primarily harmful because of their role in potentially fatal anaphylactic reactions. Nevertheless, there is also growing evidence for their contribution to human health. Animal models of bacterial infections repeatedly demonstrated that MCs played a critical role in host defence, and in some models, the presence of MCs was crucial for host survival. Data on their involvement in early responses of innate immunity to other pathogens is also increasing. The sentinel role of MCs in host defence should be considered in the light of recent data mentioned in this article while prescribing the drugs, which were demonstrated to have inhibitory effects on mast cell functions e.g. degranulation or mediator release, such as glucocorticoids, cyclosporine and cromolynes. This review summarizes newly defined functional aspects of human MCs, and emphasizes their unique role in host defence.