Most physicians prescribe Lyme disease antibiotic therapy regimens that are recommended by the Centers for Disease Control and Prevention, the Infectious Disease Society of America, and the National Institutes of Health. An alternative approach by some physicians consists of prolonged antibiotic treatment for >2 months because they believe that Lyme disease often results in persistent Borrelia burgdorferi infection. Understanding how patients perceive the disease is important for effective doctor-patient communication. We conducted interviews and surveys on Block Island, Rhode Island, and Storrs, Connecticut, to explore the public perception of persistent symptoms following Lyme disease and the need for long-term treatment. Most of our participants believed that symptoms and the Lyme disease bacteria can persist after antimicrobial therapy for Lyme disease. When asked about the value of continuing antibiotic treatment for >2 months, about half thought that it was sometimes useful and about a quarter thought it was always useful. Almost all of the respondents stated that they knew people who had experienced Lyme disease, and these personal observations were more frequently cited as an important source of Lyme disease information than official sources such as medical professionals. We conclude that healthcare workers should review the scientific literature regarding appropriate therapy for Lyme disease, discuss such information with their patients, and identify sources of information that their patients can review. Medical societies, private foundations, and State and Federal Health agencies should increase efforts to educate physicians and the general public about the standard diagnosis and treatment of Lyme disease and provide additional funding to determine why some people experience persistent symptoms following this infection.