Antigenic variation is defined as a hereditable, reversible variation in an antigenic structure that occurs during the course of infection at a rate higher than would be expected for standard recombination or mutation mechanisms. Many bacterial and protozoal pathogens have developed antigenic variation systems in which surface antigens can be continually altered as a means of evading the constant onslaught of adaptive antibody and T cell responses (1). In 1997, an elaborate antigenic variation system was identified in Borrelia burgdorferi B31 (2). Because of sequence similarity between this system and the previously characterized variable major protein (VMP) system of relapsing fever bacteria, it was termed theVMP‐likesequence (vls) locus. Its expression site, called vls Expressed (vlsE), undergoes remarkable sequence variation involving segmental gene conversion events from vls silent cassettes. This review describes what is currently known about the structure, properties, role in host‐pathogen interactions, recombination process and evolution of the vls system.