Bacillus subtilis PhoP-PhoR two-component system (TCS) senses phosphate deficiency conditions, and then controls expression of the Pho regulon to prolong survival. The sensor histidine kinase, PhoR, is autophosphorylated and transfers the phosphate to the response regulator, PhoP. Phosphorylated PhoP (PhoP~P) binds to repeated 6-bp consensus PhoP binding sequences of Pho regulon promoters and activates or represses gene expression. Pho signal transduction systems are part of interconnected signal transduction network involving at least three TCSs (PhoP-PhoR, ResD-ResE TCS, SpoOA phosphorelay), a global carbon metabolism regulator (CcpA), and transition state regulators (AbrB, ScoC). In addition, PhoP-PhoR TCS is cross related with YycF-YycG TCS by cross-regulation. While indescribable progress has been made in understanding phosphate deficiency stress response through refined expression of the Pho regulon in the recent past years, many important questions still remain. Solving these questions may provide important information for application study using B. subtilis.