This paper reviews the role of cAMP response element binding protein (CREB) signaling pathway in therapy of traditional Chinese medicine on cognitive impairment. CREB is closely related to neuronal generation,synaptic plasticity,learning and memory. Many signal transduction pathways within nerve cells can converge and involve in the induction of CREB activation. Multiple signal transduction pathways,such as cyclic adenosine monophosphate(cAMP)signaling pathway,phosphoinositide-3-kinase/ protein kinase B(PI3K/Akt)signaling pathway,p38 mitogen-activated protein kinase(p38MAPK)and calcium/ calmodulin-dependent protein kinaseⅡ(Ca,2+,-CAMKⅡ),can mediate the phosphorylation of CREB,which make the CREB signaling pathway and its related molecules become the drug targets in the treatment of cognitive impairment.