Despite more than 25 years' experience with Lyme borreliosis, much remains to be learned about this complex zoonosis. Practicing veterinarians, particularly those in the northeastern and upper midwestern states, where Lyme borreliosis is highly endemic, should be familiar with the ecologic features and typical clinical signs of Lyme borreliosis. Interpretation of signs and serologic test results should be made with consideration of the regional prevalence of Lyme borreliosis and the animal's opportunity for exposure to infected Ixodes spp. The availability of recently marketed topical acaracides is a valuable adjunctive measure in prevention of Lyme borreliosis. A maximally effective prevention strategy should include consideration of environmental modification, activity restrictions, routine examinations for ticks, prompt removal of attached ticks, and vaccination. Technologic advances, such as the C6 EIA and the Osp A recombinant vaccine, offer the promise of additional tools for the clinical management and prevention of this tick-borne zoonosis.