Lyme disease also called Lyme borreliosis is a multisystem illness caused by the spirochete Borrelia burgdorferi. The primary care provider’s role is paramount in the diagnosis and treatment of Lyme disease, as early diagnosis and treatment translate into better outcomes. The best opportunity for an accurate early diagnosis is the characteristic erythema migrans (EM) or bull’s-eye rash stage. The manifestation of early disseminated and late Lyme disease can affect personal, professional, or social aspects of a patient’s life regardless of response to treatment. Varying degrees of fatigue, malaise, memory loss, concentration difficulties, anxiety, and depression often accompany dissemination and neurologic involvement. The primary care provider must recognize and address the possible complications of Lyme disease and their potential effects on the patient. Information on available support groups and psychological counseling if indicated should be provided.