Many tick-borne infections are increasing in geographic range as a result of activities such as reforestation and climate change. A history of outdoor activity in tick-endemic regions, together with consistent clinical signs (such as fever, splenomegaly, polyarthritis, thrombocytopenia), should raise suspicion for tick-borne infectious disease. Diseases with short incubation periods are best diagnosed with organism-detection assays. When the incubation period is long and organism numbers are low, diagnosis often relies on antibody testing, but it may be difficult to associate positive tests with infection. Positive antibody tests in healthy animals should prompt veterinarians to discuss prevention approaches with owners.