Hydrogen sulfide (H2S) has long been known as a toxic gas. However, recently accumulated evidence suggests that H2S contributes to a variety of physiologic and pathologic processes. Endogenous H2S production is regulated by multiple enzymes that are differentially expressed in the cardiovascular, neuronal, immune, renal, respiratory, gastrointestinal, reproductive, liver, and endocrine systems. Alteration of H2S metabolism may affect multiple signaling pathways and tissue homeostasis. The growing number of diverse targets for which H2S serves as a gasotransmitter has been extensively reviewed elsewhere. In this review, the authors discuss current emerging evidence that H2S regulates mesenchymal stem cell and T-cell functions. © International & American Associations for Dental Research 2016.