Publisher Summary This chapter focuses on the lower forms of life—that is, single-celled organisms. It briefly reviews the literature on cyclic guanosine monophosphate (cGMP) in bacteria and then describes two systems that have been studied frequently—the slime mold (Dictyostelium discoideum) and the protozoans (Paramecium and Tetrahymena). The chapter explores the evolution of the cGMP system that developed as a distinct-regulatory system. The chapter explains the kind of functions that are affected and regulated by those primordial cGMP systems. It compares enzymes of cGMP metabolism such as guanylyl cyclase and cGMP phosphodiesterase from lower organisms with those isolated and cloned from mammals.