Homeostasis is an essential capability of all cells mediated by complex and diverse regulatory networks. Despite this complexity, many of the fundamental regulatory mechanisms used by cells have been evolutionarily conserved. It is thus somewhat surprising that the apparent physiologic significance of these mechanisms has been experimentally neglected. Here, we review 2 widely recognized regulatory mechanisms, allostery and compartmentalization, which exemplify this dissociation in our current understanding of the microbial pathogen, Mycobacterium tuberculosis.