Bacterial physiology is enjoying a renaissance in the postgenomic era as investigators struggle to interpret the wealth of new data that has emerged and continues to emerge from genome sequencing projects and from analyses of bacterial gene regulation patterns using whole-genome methods at the transcriptional and posttranscriptional levels. Information from model organisms such as the Gram-negative bacterium Escherichia coli is proving to be invaluable in providing points of reference for such studies. An important feature of this work concerns the nature of global mechanisms of gene regulation where a relatively small number of regulatory proteins affect the expression of scores of genes simultaneously. The nucleoid-associated proteins, especially Factor for Inversion Stimulation (Fis), IHF, H-NS, HU, and Lrp, represent a prominent group of global regulators and studies of these proteins and their roles in bacterial physiology are providing new insights into how the bacterium governs gene expression in ways that maximize its competitive advantage.