Cytokinins are essential plant hormones that control cell division, shoot meristem initiation, leaf and root differentiation, vasculature patterning, chloroplast biogenesis, photomorphogenesis, fertility, seed development, senescence, and stress tolerance. The Arabidopsis cytokinin signal transduction pathway involves hybrid histidine protein kinases [AHK2, AHK3, and AHK4 (also known as CRE1or WOL)] as cytokinin receptors, histidine phosphotransfer proteins (AHPs), and nuclear response regulators (ARRs) that serve as transcriptional regulators. There are four major steps in the cytokinin phosphorelay: (i) AHK sensing and signaling, (ii) AHP nuclear translocation, (iii) ARR-dependent transcriptional activation, and (iv) a negative-feedback loop through cytokinin-inducible ARR gene products. Each step is executed by components encoded by multigene families. The effects of cytokinin depend on cell type, environment, and developmental stage. The response is frequently the outcome of interactions with other plant signaling pathways.