Blood-feeding arthropods transmit numerous types of infectious agent and parasite that have a tremendous impact on human health and mortality throughout the world. These vector-borne pathogens display a wide array of evolutionary patterns that allow them to infect and to be successfully transmitted by ticks, mites, and hematophagous insects. The vector's method of feeding, type of development, and host preference are also critical factors for the transfer of zoonotic agents from wild animal reservoirs to susceptible humans. Ticks are obligate blood-feeders in all life stages and biologically transmit many infectious agents. In North America, two ticks that are involved in the maintenance and transmission of pathogenic spirochetes include Ixodes scapularis (family Ixodidae) and Ornithodoros hermsi (family Argasidae). These ticks are the respective vectors of the Lyme disease spirochete Borrelia burgdorferi and a relapsing fever spirochete, Borrelia hermsii. Little is known concerning how these and related species of Borrelia adapt to successfully alternate between warm-blooded vertebrates and ticks; however, the possibility that borrelial surface proteins are differentially expressed in their different hosts is an exciting area of current research.