Mast cells are immune cells of the haematopoietic lineage that are now thought to have multifaceted functions during homeostasis and in various disease states. Furthermore, while mast cells have been known for a long time to contribute to allergic disease in adults, recent studies, mainly in mice, have highlighted their early origins during fetal development and potential for immune functions, including allergic responses, in early life. Our understanding of the imprinting of mast cells by particular tissues of residence and their potential for regulatory interactions with organ systems such as the peripheral immune, nervous and vascular systems is also rapidly evolving. Here, we discuss the origins of mast cells and their diverse and plastic phenotypes that are influenced by tissue residence. We explore how divergent phenotypes and functions might result from both their hard-wired ‘nature’ defined by their ontogeny and the ‘nurture’ they receive within specialized tissue microenvironments.