cGMP is used as a second messenger in many eukaryotes. cGMP signaling requires at least three components: Guanylyl cyclases synthesize cGMP from GTP. Specific cGMP-binding proteins propagate the signal, usually by phosphorylation of their target proteins. Finally, phosphodiesterases terminate the cGMP signal by hydrolyzing cGMP to 5'cGMP. Recently, all guanylyl cyclases and most of the cGMP target proteins and phosphodiesterases of the cellular slime mold Dictyostelium discoideum have been identified. Characterization of these enzymes show them to be structurally and evolutionarily distinct from their bacterial and metazoan counterparts. In this chapter we review the properties of the Dictyostelium guanylyl cyclases and discuss their role in the unusual cGMP pathway of Dictyostelium.