A bacterial genome encodes thousands of different proteins needed to handle many different environmental contingencies. Some proteins, such as RNA polymerase, are always required for growth; these are called “housekeeping proteins.” Most proteins, however, are needed only under a limited set of conditions. Proteins that degrade the sugar lactose, for example, are only useful when lactose is present. Likewise, Virbio cholerae needs to make cholera toxin only when it is growing inside the human body, not when it is living in the ocean. To compete successfully with others, the microbe will not waste energy making unneeded proteins. Cells achieve molecular efficiency using elegant control systems that selectively increase or decrease gene transcription, mRNA translation, or mRNA degradation, as well as by degrading or sequestering regulatory proteins. This chapter explores the how and why of molecular regulation and introduces new technologies that allow us to understand the dynamic transcriptome and proteome.