The Borrelia are widely distributed agents of Lyme disease and Relapsing Fever. All are vector-borne zoonotic pathogens, have segmented genomes, and enigmatic mechanisms of pathogenesis. Adhesion to mammalian and tick substrates is one pathogenic mechanism that has been widely studied. At this point, the primary focus of research in this area has been on Borrelia burgdorferi, one agent of Lyme disease, but many of the adhesins of B. burgdorferi are conserved in other Lyme disease agents, and some are conserved in the Relapsing Fever Borrelia. B. burgdorferi adhesins that mediate attachment to cell-surface molecules may influence the host response to the bacteria, while adhesins that mediate attachment to soluble proteins or extracellular matrix components may cloak the bacterial surface from recognition by the host immune system as well as facilitate colonization of tissues. While targeted mutations in the genes encoding some adhesins have been shown to affect the infectivity and pathogenicity of B. burgdorferi, much work remains to be done to understand the roles of the adhesins in promoting the persistent infection required to maintain the bacteria in reservoir hosts.