The ability of many genes to be induced by cAMP is dependent on the presence of enhancers located in the regions of DNA upstream of the start sites to the genes. The two best characterized enhancers are the CRE (5'-TGACGTCA-3') and the AP-2 site (5'-CCCCAGGC-3'). The activity of the CRE is modulated by sequences adjacent to the consensus sequence as well as by promoter context and cell type. The complex control of the CRE is reflected in the large number of cloned CRE binding proteins that arise both from unique genes and from splice variants. These factors are leucine zipper proteins that must dimerize before binding to DNA. Although all of the factors isolated can form active homodimers, many are also able to form heterodimers. The amino termini of these proteins contain consensus phosphorylation sites through which these factors trans-activate their cognate promoters. The diversity of the trans-acting factors and their cis-acting sequences reflects the precise control that cells require in the modulation of gene expression by cAMP.