Depletion of nutrients, including phosphate, is a stress often encountered by a bacterial cell, and results in slowed growth, marking the cessation of exponential growth. Genes that are transcriptionally activated during phosphate starvation have been used to examine the signal-transduction mechanisms governing the Pho regulon in Bacillus subtilis. Alkaline phosphatase, the traditional reporter protein for Pho regulation in prokaryotes, is encoded by a multigene family in B. subtilis. Characterization of the alkaline phosphatase family was a breakthrough in the study of regulation of the Pho regulon, especially the discovery of promoter elements exclusively responsive to phosphate-starvation regulation. Current data suggest that at least three two-component signal-transduction systems interact, forming a regulatory network that controls the phosphate-deficiency response in B. subtilis. The interconnected pathways involve the PhoP–PhoR system, whose primary role is to mediate the phosphate-deficiency response; the Spo0 phosphorelay required for the initiation of sporulation; and a newly discovered signal-transduction system, ResD–ResE, which also has a role in respiratory regulation during late growth. Parallel pathways positively regulate the Pho response via PhoP–PhoR. One pathway includes the ResD–ResE system, while the other involves a transition-state regulator, AbrB. The Spo0 system represses the Pho response by negatively regulating both pathways. This review will discuss how the characterization of the APase multigene family made possible studies which show that the Pho regulon in B. subtilis is regulated by the integrated action of the Res, Pho and Spo signal-transduction systems.