CREB and its relatives are widely recognized as stimulus-inducible transcription factors. In neurons, various extracellular stimuli can activate CREB family members, and CREB-dependent gene expression is involved in processes such as development, plasticity, and disease. This review focuses on the current understanding of CREB family members' roles in the nervous system. CREB belongs to the bZIP superfamily of transcription factors and includes CREM and ATF-1. These factors contain a basic domain for DNA binding and a leucine zipper domain for dimerization. CREB family members can function as activators or repressors depending on exon usage. The most abundant CREB isoforms, CREBα and CREBΔ, contain the bZIP domain and two glutamine-rich domains. Phosphorylation of Ser-133 in the KID domain is critical for CREB's interaction with the coactivator CBP, which is essential for inducible gene expression. CREB is activated by a wide range of physiological stimuli, leading to new gene transcription and diverse cellular responses. In the nervous system, CREB is involved in neuronal survival, proliferation, differentiation, and process outgrowth. CREB is required for proper nervous system development, and its absence leads to neuronal loss and death. CREB and CREM are both essential for neuronal survival at late embryonic and postnatal stages. CREB is also involved in learning, memory, and synaptic plasticity. Studies in Aplysia and Drosophila have shown that CREB plays a role in learning and memory in invertebrates. In vertebrates, CREB is involved in learning and memory, and its function is critical for long-term memory and plasticity. However, its requirement for plasticity is not absolute, as some studies suggest that other family members can compensate. CREB is also involved in addiction, with CREB-dependent gene expression implicated in the long-term neuronal changes associated with addiction. CREB is activated in response to substances of abuse and is involved in the development of addiction. The regulation of CREB phosphorylation and function varies depending on the substance and CNS region involved. CREB is involved in circadian rhythms, with CREB-dependent gene expression playing a role in the entrainment of the circadian clock. CREB is also involved in neuroprotection and disease, with CREB-dependent gene expression contributing to neuronal survival under stressful conditions. Disruption of CREB function can lead to severe consequences, including neurodegenerative diseases such as Huntington's disease. CREB target genes include genes involved in neurotransmission, cell structure, signal transduction, transcription, and metabolism. The specificity of CREB-dependent gene expression is influenced by the interaction of CREB with other transcription factors and coactivators. CREB signaling is regulated by various kinases, including PKA, CaMKs, and the Ras/ERK pathway, which are involved in the phosphorylation of CRECREB and its relatives are widely recognized as stimulus-inducible transcription factors. In neurons, various extracellular stimuli can activate CREB family members, and CREB-dependent gene expression is involved in processes such as development, plasticity, and disease. This review focuses on the current understanding of CREB family members' roles in the nervous system. CREB belongs to the bZIP superfamily of transcription factors and includes CREM and ATF-1. These factors contain a basic domain for DNA binding and a leucine zipper domain for dimerization. CREB family members can function as activators or repressors depending on exon usage. The most abundant CREB isoforms, CREBα and CREBΔ, contain the bZIP domain and two glutamine-rich domains. Phosphorylation of Ser-133 in the KID domain is critical for CREB's interaction with the coactivator CBP, which is essential for inducible gene expression. CREB is activated by a wide range of physiological stimuli, leading to new gene transcription and diverse cellular responses. In the nervous system, CREB is involved in neuronal survival, proliferation, differentiation, and process outgrowth. CREB is required for proper nervous system development, and its absence leads to neuronal loss and death. CREB and CREM are both essential for neuronal survival at late embryonic and postnatal stages. CREB is also involved in learning, memory, and synaptic plasticity. Studies in Aplysia and Drosophila have shown that CREB plays a role in learning and memory in invertebrates. In vertebrates, CREB is involved in learning and memory, and its function is critical for long-term memory and plasticity. However, its requirement for plasticity is not absolute, as some studies suggest that other family members can compensate. CREB is also involved in addiction, with CREB-dependent gene expression implicated in the long-term neuronal changes associated with addiction. CREB is activated in response to substances of abuse and is involved in the development of addiction. The regulation of CREB phosphorylation and function varies depending on the substance and CNS region involved. CREB is involved in circadian rhythms, with CREB-dependent gene expression playing a role in the entrainment of the circadian clock. CREB is also involved in neuroprotection and disease, with CREB-dependent gene expression contributing to neuronal survival under stressful conditions. Disruption of CREB function can lead to severe consequences, including neurodegenerative diseases such as Huntington's disease. CREB target genes include genes involved in neurotransmission, cell structure, signal transduction, transcription, and metabolism. The specificity of CREB-dependent gene expression is influenced by the interaction of CREB with other transcription factors and coactivators. CREB signaling is regulated by various kinases, including PKA, CaMKs, and the Ras/ERK pathway, which are involved in the phosphorylation of CRE