Bacteria grow when nutrient availability supports basic biochemical requirements and remain in stationary phase when basic needs go unmet. This deceptively simple phenomenon requires the orchestrated expression of thousands of genes. Free-living bacteria use a nucleotide second messenger, ppGpp, as a physiological signal and effector to appropriately coordinate global gene expression according to the nutritional quality of the environment. Over the last four decades, expression of many individual genes has been tied to the absence or presence of ppGpp, yet the full scope of gene expression mediated by ppGpp remained undefined. This dissertation defines the role of ppGpp in regulating global gene expression in a model bacterium, Escherichia coli.