Outer membrane vesicles (blebs) are produced by Escherichia coli, Salmonella, and all other gram-negative bacteria both in vitro and in vivo. Most of the research in the field has focused on the properties of vesicles derived from pathogenic bacteria and their interactions with eukaryotic cells. These data indicate that vesicles are able to contribute to pathogenesis. Thus, it appears that pathogenic gram-negative bacteria have co-opted vesicles for the dissemination of virulence determinants. However, the role of vesicle production by nonpathogenic bacteria is less obvious. This section reviews the data demonstrating the mechanistic and physiological basis of outer membrane vesicle production by bacteria. Vesiculation can be seen as a mechanism for cells to react to conditions in the surrounding environment by carrying away unnecessary components and allowing rapid modification of the outer membrane composition. In addition, vesicles can transmit biological activities distant from the originating cell. Vesicles could act to bind and deplete host immune factors at the site of infection that would otherwise attack the bacteria. Vesicles in the area surrounding the cell may also provide the cell protection inside a human or animal host. The concept of vesicles as virulence factors has received considerable attention, and they are likely to play a significant role in the pathogenesis of gram-negative bacteria. By analysis of their composition, mechanism of formation, regulation, and physiological function, progress is being made in understanding the ubiquitous nature of outer membrane vesicles produced by gram-negative bacteria.