Stomatal density, spacing, and patterning greatly influence the efficiency of gas exchange, photosynthesis, and water economy. They are regulated by a complex of extracellular and intracellular factors through the signaling pathways. After binding the extracellular epidermal patterning factor 1 (EPF1) and 2 (EPF2) as ligands, the receptor-ligand complexes activate by phosphorylation through the MAP-kinase cascades, regulating basic helix-loop-helix (bHLH) transcription factors SPEECHLESS (SPCH), MUTE, and FAMA. In this review, we summarize the molecular mechanisms and signal transduction pathways running within the transition of the protodermal cell into a pair of guard cells with a space (aperture) between them, called a stoma, comprising asymmetric and symmetric cell divisions and draw several functional models. The feedback mechanisms involving the bHLH factors SPCH and MUTE are not fully recognized yet. We show the feedback mechanisms driven by SPCH and MUTE in the regulation of EPF2 and the ERECTA family. Intersections of the molecular mechanisms for fate determination of stomatal lineage cells with the role of core cell cycle-related genes and stabilization of SPCH and MUTE are also reported.