The global transcriptional regulator CtrA controls multiple events in the Caulobacter cell cycle, including the initiation of DNA replication, DNA methylation, cell division, and flagellar biogenesis. CtrA is a member of the response regulator family of two component signal transduction systems and is activated by phosphorylation. We report here that this phosphorylation signal enters the cell cycle at mid S phase. In addition, CtrA function is modulated by temporally and spatially controlled proteolysis. When an active CtrA protein is present at the wrong time in the cell cycle, owing to expression of a mutant CtrA derivative that is active in the absence of phosphorylation and is not turned over during the cell cycle, the G1-to-S transition is blocked and the cell cycle aborts. Thus, both phosphorylation and proteolysis are critical determinants of bacterial cell cycle control in a manner that is analogous to the control of the eukaryotic cell cycle.