Cytokinins regulate various events in plant development according to the intrinsic developmental program and in response to environmental stimuli. Recent genetic and molecular biological studies have revealed the framework of the intracellular signal transduction pathway from cytokinin perception to transcriptional regulation of primary cytokinin-responsive genes in Arabidopsis thaliana. Membrane-bound histidine kinases, including CRE1/AHK4, AHK2, and AHK3, perceive cytokinins. The signal is then transferred via histidine-containing phosphotransfer factors, AHPs, to transcription-factor-type response regulators, such as ARR1, which execute the signal-dependent transactivation of primary cytokinin-responsive genes, including those for other types of response regulator. Simply stated, the cytokinin signal is mediated by the His-Asp phosphorelay, which was originally found in bacterial two-component regulatory systems. However, many details, especially those that are essential for elucidating the regulatory mechanisms underlying complicated cytokinin responses, remain unknown.