One central microbiological question is what factors change the size and content of bacterial genomes. What causes such genomes to become smaller for microbes that live as intracellular parasites or as symbionts, and what novel functions do they incorporate and stably maintain? From comparative sequence analyses during the past decade, we know that the gene content of bacterial genomes is in flux over both short intervals and longer periods, affected by several dynamic processes, including horizontal gene transfer, gene duplications, gene fusions, and gene losses (Fig. 1). Thus, for example, the ancestors of Escherichia coli K12 and O157:H7 were subject to repeated horizontal gene transfers, while there are signs of extensive gene amplification in Orientia tsutsugamushi, and massive gene loss in the free-living γ-proteobacterial ancestors of Buchnera and Carsonella ruddii.