Borrelia burgdorferi, the spirochete that causes Lyme disease, has evolved elegant strategies for interacting with its mammalian hosts. Among them are several distinct mechanisms of adhesion to 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 β 3-chain integrins. This diversity of adhesion mechanisms allows B. burgdorferi to infect multiple tissues, including the synovial tissues of the joints.