Mast cells (MCs) have been intensely investigated over the past two decades, e.g. the numbers of PubMed-listed reports on MCs have steadily increased and doubled over the past twenty years. Surprisingly, many recent findings that have fundamentally changed our understanding of MC biology and functions have yet to be sufficiently recognized by scientists interested in cutaneous biology and clinical dermatologists. The aim of this study is to review recent hallmark contributions to the field of MC research, to outline the development of our current knowledge of MCs, and to predict the outcome of future MC research efforts. The development of straightforward rodent in vivo models has allowed for the identification and characterization of various novel MC functions. MC effects are not limited to the induction of pathology, but can serve important functions in maintaining health and preventing disease. Attempts to better define the role of MCs in the human system may lead to novel strategies for treating inflammatory disorders and could eventually allow us to utilize MCs for improving responses to environmental danger signals.