Most current paradigms of microbial metabolism have been derived from studying cells grown under a variety of nutrient compositions in aqueous environments. With recent advances in genomics and experimental techniques, alternative forms of bacterial growth are increasingly being explored. When propagated on nutrient-rich semi-solid media, several species of bacteria undergo a morphological differentiation into swarmers that are capable of migrating on surfaces. Recent studies indicate that swarmer differentiation represents much more than a motility phenotype, as several clinically important attributes are also co-regulated. We demonstrate that migrating swarmer cells of Salmonella are metabolically differentiated compared to the vegetative swimmer cells grown in the same nutrient environment. Furthermore, once the cells have differentiated, the swarmers remain in this physiological state under conditions that do not promote the initial differentiation. The bacterium's capacity to override some of the classic paradigms of metabolic regulation established in aqueous environments represents a unique physiological response by the pathogen that may be advantageous in polymicrobial environments such as the host.