Being metabolic regulators, nucleotides play many other roles rather than just providing the alphabets of the genetic code. The pyrimidine bases act as identifiers for metabolites. Purine nucleotides play their main regulatory roles in association with proteins, not metabolites. The current terminology of GTP-binding proteins embraces G proteins and GTPases. All are capable of hydrolysing GTP, so technically all are GTPases. The term G protein is generally reserved for the class of GTP-binding proteins that interact with 7TM receptors. All of these are composed of three subunits, α, β, and γ, and so it is also common to refer to the heterotrimeric G proteins. The basic cycle of GTP binding and GTP hydrolysis, switching them between active and inactive states, is common to all of them and it is coupled to many diverse cellular functions. It was initially surprising to find that the rate of GTP hydrolysis catalysed by isolated G proteins is far too slow to account for the transient nature of some of the known G-protein-mediated responses. It is now clear that the rate of the GTPase reaction is stepped up very considerably as soon as activated α-subunits come into contact with effector enzymes. The βγ-subunits also serve to present negative feedback signals as demonstrated first through the activation of rhodopsin kinase and later with GRK2/β-adrenergic receptor kinase. It must be evident that the whole sequence of control, from the first interaction of a hormone with its receptor right through to the generation of second messengers, and then back again to the receptors, is tightly regulated at all stages. Throughout, it remains flexibly sensitive to the needs of the cell.