Lyme disease is the most common vector-borne disease in the United States. Diagnosis is problematic for many reasons, including unsatisfactory laboratory tests and confusion about test interpretation. When Lyme disease is diagnosed early, treatment is usually successful with oral antibiotics. Unfortunately, the diagnosis is often missed, allowing the infection to disseminate and affect every body system. When Lyme disease affects the central nervous system, it is often treated with intravenous antibiotics in the home setting. Infusion nurses who are experienced with the myriad symptoms and treatment challenges of these complex patients will be a reassuring asset to patients and physicians alike.