The cAMP-protein kinase A (PKA) pathway is an important intracellular signal transduction cascade that can be activated by a large variety of stimuli. Activation or inhibition of this pathway will ultimately affect the transcriptional regulation of various genes through distinct responsive sites. In vertebrates, the best- characterized nuclear targets of PKA are the cyclic AMP response element-binding (CREB) proteins. It is now well established that CREB is not only regulated by PKA, but many other kinases can exert an effect as well. Since CREB-like proteins were also discovered in invertebrates, several studies unraveling their physiological functions in this category of metazoans have been performed. This review will mainly focus on the presence and regulation of CREB proteins in insects. Differences in transcriptional responses to the PKA pathway and other CREB-regulating stimuli between cells, tissues, and even organisms can be partially attributed to the presence of different CREB isoforms. In addition, the regulation of CREB appears to show some important differences between insects and vertebrates. Since CREB is a basic leucine zipper (bZip) protein, other insect members of this important family of transcriptional regulators will be briefly discussed as well