The morphogene bolA plays a significant role in the adaptation of Escherichia coli to general stresses. In general, bacteria can thrive and persist under harsh conditions, counteracting external stresses by using varied mechanisms, including biofilm formation, changes in cell shape, size and protein content, together with alterations in the cell wall structure, thickness and permeability. In E. coli, an increased expression of bolA occurs mainly under stress challenges and when bacterial morphology changes from rod-like to spherical. Moreover, BolA is able to induce biofilm formation and changes in the outer membrane, making it less permeable to harmful agents. Although there has been substantial progress in the description of BolA activity, its role on global cell physiology is still incomplete. Proteins with strong homology to BolA have been found in most living organisms, in many cases also exerting a regulatory role. In this review we summarize current knowledge on the role of BolA, mainly in E. coli, and discuss its implication in global regulation in relation to stress.