Runx3, a member of the Runt-related transcription factor family, has attracted extensive attention due to its important role in the development of immune systems, especially in the differentiation of T cells. Accumulated evidence indicated that altered expression of Runx3 regulates a variety of target genes in different tissues/cells. Studies in animal models suggested that Runx3 may regulate the development of T cell lineage including those of innate lymphoid cells, Treg cells and dendritic cells, which may contribute to the development of hypersensitivity and asthma. Specifically, Runx3 modulates Th1/Th2 balance and hence, the production of interleukins, which induce inflammatory responses. Understanding the roles and mechanisms of Runx3 in the regulation of immune function provides a basis for the design of novel preventive and treatment models for bronchial asthma. This article reviews published data from cell lines, animal models, and patients, concerning the relationship between Runx3 expression alteration and asthma. Epigenetic regulation of Runx3 by DNA hypermethylation and microRNA, and the implication of these pathways in asthma are also discussed.