In the two years after publication of the genome sequence of Borrelia burgdorferi and reports on human field trials of a vaccine against Lyme borreliosis, there has been further progress in understanding of host-parasite interactions during Lyme borreliosis and relapsing fever. Some mechanisms that Borrelia spirochetes use to avoid elimination and to persist in the host are novel. In addition, the recent discovery of antigenic variation in the Lyme disease agent B. burgdorferi adds to the complexity of the possible virulence properties of this human pathogen.