The two-component signaling systems (TCSs), which mediate the histidine-aspartate signaling, control diverse biological processes of many organisms, including cell division, cell growth and proliferation and responses to environmental stimuli and growth regulators. We have provided in planta evidence that the cytokinin (CK) responsive TCS mediates abscisic acid (ABA) and osmotic stress responses. By using loss-of-function approach we have demonstrated that the three cytokinin (CK) receptor histidine kinases AHK2, AHK3 and AHK4/CRE1 act as negative regulators in ABA, drought and high salinity stress signalings. Genome-wide expression profiling of the stress-tolerant <ahk2,3> double mutant suggested that CK receptor kinases mediate osmotic stress response in both an ABA-dependent and ABA-independent manner. Additionally, we showed evidence for the role of CK in mediating stress responses, judging from the fact that AHK4 requires the CK to function as a negative regulator in osmotic stress response. Our results suggested that cross-talk exists among CK, ABA and osmotic stress signaling pathways, and that CK signaling and CK metabolism may play crucial roles not only in plant growth and development but also in osmotic stress signaling.