Since the cloning of the somatostatin cDNA and gene, the efforts of a number of laboratories have contributed to the understanding of somatostatin gene expression and regulation. A genetic element located approximately 40 nucleotides upstream from the somatostatin mRNA cap site is important in the expression and cAMP-induced transcription of this neuropeptide gene. The identification of this genetic element has enabled the identification, purification, and cloning of a new class of proteins: the somatostatin gene transactivator named CREB. The availability of cloned CREB will permit studies designed to understand not only the mechanism of somatostatin gene expression and regulation, but also the pathway of signal transduction triggered by cAMP-stimulated events.