Guanosine 3′5′ cyclic monophosphate (cGMP) mediates a wide variety of physiological processes in many invertebrate and vertebrate species. Here we discuss our current understanding of cGMP regulation and function in insects, reviewing components of the cGMP signaling cascade and some of the major physiological roles played by cGMP in insects. The recent completion of the Drosophila genome project has enabled us to identify all the potential elements of the cGMP signaling cascade in a single insect. Most of these proteins have not been previously characterized, and by comparing their predicted sequences with identified proteins from other species (insects and mammals) we describe their expected properties. The list of potential proteins that regulate cGMP levels includes five receptor guanylyl cyclases (GCs), two receptor-like GCs, five soluble GC subunits, a possible GC-activating peptide, five possible GCAP-like proteins and five phosphodiesterases that are predicted to hydrolyze cGMP. Downstream elements of cGMP signaling include two phosphodiesterases that could be regulated by cGMP, three cGMP-dependent protein kinases and two ion channels that could be regulated by cGMP.