Differentiation of vegetative Bacillus subtilis into heat resistant spores is initiated by the activation of the key transcription regulator Spo0A through the phosphorelay. Subsequent events depend on the cell compartment-specific action of a series of RNA polymerase sigma factors. Analysis of genes in the Spo0A regulon has helped delineate the mechanisms of axial chromatin formation and asymmetric division. There have been considerable advances in our understanding of critical controls that act to regulate the phosphorelay and to activate the sigma factors.