Many mechanisms of gene regulation in bacteria do not employ repressor or activator proteins. One class of these mechanisms includes those in which the key regulatory element is the control of transcription initiation by the availability of NTP substrates. In this commentary, several distinct examples of initiating NTP-mediated gene regulation are discussed, including a mechanism reported by Krásný et al. in this issue of Molecular Microbiology. These researchers show that during the stringent response induced by amino acid starvation of Bacillus subtilis, increases in the intracellular level of ATP permit upregulation of promoters with +1A start sites, while concurrent decreases in the intracellular level of GTP cause downregulation of promoters with +1G start sites. This regulation is restricted to stringently controlled promoters.