Our knowledge of Lyme disease, currently the most common vector-borne illness in North America, has expanded over the past decade. The causative spirochete, Borrelia burgdorferi, is transmitted by the bite of an infected Ixodes tick. Infection usually results in erythema migrans and can spread hematogenously to skin, heart, nervous system, joints, and other organs. Prompt recognition and treatment with antibiotics usually leads to rapid improvement and markedly reduces subsequent manifestation. Unrecognized and untreated Lyme disease can cause late arthritic and neurologic syndromes that are more difficult to treat and that may not respond to antibiotics. Other tick-borne illnesses can be fatal if not treated.