Outer membrane protein A (OmpA) is an abundant protein of Escherichia coli and other enterobacteria and has a multitude of functions. Although the structural features and porin function of OmpA have been well studied, its role in the pathogenesis of various bacterial infections has emerged only during the last decade. The four extracellular loops of OmpA interact with a variety of host tissues for adhesion to and invasion of the cell and for evasion of host-defense mechanisms when inside the cell. This review describes how various regions present in the extracellular loops of OmpA contribute to the pathogenesis of neonatal meningitis induced by E. coli K1 and to many other functions. In addition, the function of OmpA-like proteins, such as OprF of Pseudomonas aeruginosa, is discussed.