PKG (cGMP-dependent protein kinase) is a major intracellular receptor for cGMP and mediates a range of downstream physiological functions. Although most studies have concentrated on mammalian isoforms, the advent of whole genome sequencing has lead to identification of orthologues from other diverse species. Many biochemical and regulatory properties and structural features of PKG have been conserved throughout evolution. However, in protozoa there can be variation in the number of cGMP-binding sites and a tendency toward degeneracy of these additional sites. Recent work on the protozoan PKGs is the major focus of this review. Important functional data are emerging for these and other non-mammalian isoforms. Intriguingly, a role for PKG in locomotion is becoming a common functional theme across diverse phyla.