Lyme disease is the most common vector-borne infection reported in the United States, where most cases are caused by the spirochete Borrelia burgdorferi following transmission from the black-legged or deer tick (Ixodes scapularis). Its most common clinical sign is the erythema migrans or “bull’s eye” rash. Other common manifestations include meningitis, carditis, cranial neuropathy, and arthritis. For those with later manifestations of Lyme disease, serology can be helpful in diagnosis. Lyme disease responds well to antibiotics, treated most often with doxycycline or amoxicillin. A small subset of patients, mostly adults, experience nonspecific symptoms following antibiotic treatment due to posttreatment Lyme disease syndrome, a noninfectious complication likely the result of immune dysregulation.