The class Alphaproteobacteria includes Gram-negative free-living, symbiotic and obligate intracellular bacteria, as well as important plant, animal and human pathogens. Recent work has established the key antagonistic roles that phosphorylated guanosines, cyclic-di-GMP (c-di-GMP) and the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively referred to as (p)ppGpp), have in the regulation of the cell cycle in these bacteria. In this Review, we discuss the insights that have been gained into the regulation of the initiation of DNA replication and cytokinesis by these second messengers, with a particular focus on the cell cycle of Caulobacter crescentus. We explore how the fluctuating levels of c-di-GMP and (p)ppGpp during the progression of the cell cycle and under conditions of stress control the synthesis and proteolysis of key regulators of the cell cycle. As these signals also promote bacterial interactions with host cells, the enzymes that control (p)ppGpp and c-di-GMP are attractive antibacterial targets.