In recent years, the emerging concept of bronchial inflammation as a prominent histopathologic characteristic of asthma has profoundly modified the view of the role of the mast cell, which was traditionally thought to be linked to the release of soluble chemical mediators substantially involved in the genesis of acute, immediate bronchospasm. The finding that the production of proinflammatory cytokines by mast cells in asthmatic airways is comparable, in some circumstances, to that of T-cell origin, has led to the hypothesis that mast cells, along with T lymphocytes and eosinophils, may also contribute to the genesis of chronic, persistent asthma. This hypothesis is further supported by the finding that mast cells are able to functionally interact with B cells (promoting IgE synthesis) and T lymphocytes (acting as antigen presenting cells), thus taking part in the immune network. Moreover, mast cells produce an exclusive family of proteases (tryptases and chymases) that exert many biological actions relevant to airways inflammation and remodeling. Future studies will better explain the role of mast cells in asthma and, more specifically, the links with bone marrow—where mast cell progenitors originate—and the airways, where mast cells develop, differentiate, and assume the functions of mature cells. This article reviews recent data available on these topics.