Borrelia burgdorferi (sensu lato), the spirochete that causes Lyme disease, is among the most fascinating and enigmatic of bacterial pathogens. An obligate parasite of other organisms, B. burgdorferi is maintained in the mammalian reservoir (small rodents) by tick-mediated transmission from infected individuals to other members of the population. The complex requirements that must be met to ensure survival in an immunocompetent rodent and in the tick vector, coupled with a relatively small genome, suggest that B. burgdorferi has evolved elegant strategies for interacting with its hosts. Among these strategies are several distinct mechanisms of adhesion to mammalian cells and extracellular matrix components. The mammalian receptors for B. burgdorferi that have been most thoroughly studied, and for which candidate bacterial ligands have been identified, are decorin, fibronectin, glycosaminoglycans, and beta3-chain integrins.