Abstract: Nervous system diseases have become one of the main threats to human health due to the complexity of their pathogenesis, which has brought a heavy economic burden to society and patients themselves. So far, the etiology and pathogenesis of most neurological diseases have not been fully elucidated. Therefore, the study of neurological disease-related molecules is particularly important for the diagnosis and treatment of the diseases. CREB is a transcriptional transduction factor for intracellular cAMP changes, and its major function is to regulate gene transcription and protein synthesis. As an important nuclear regulatory factor, CREB regulates transcription through its own phosphorylation and dephosphorylation. At present, a large number of studies have shown that CREB has an important regulatory role in the nervous system such as synaptic plasticity, learning and memory, and early brain injury. The role of CREB in the nervous system is to terminate and meet many signaling pathways. The regulatory signal molecules and their target genes and CREB are involved in a variety of normal physiological activities, such as neural stem cell proliferation, cell cycle regulation, neuron-induced differentiation, and learning and memory. Therefore, CREB signaling pathway-related molecules has become a more concerned potential drug intervention target for neurological diseases. This article summarizes the structure of CREB and its transcription factor family, the regulating mechanism of CREB related signaling pathways, and its application in central nervous system diseases such as, memory disorders, epilepsy, cerebral ischemia-reperfusion injury and hemorrhagic cerebrovascular disease, alcohol addiction and Parkinson's disease. This review provides a new way to understand the pathogenesis of neurological diseases and the selection of clinical therapeutic targets.