Although Lyme disease has spread rapidly and it is difficult to diagnose, a review of the dental literature does not reveal many references to this illness. Dental practitioners must be aware of the systemic effects of this often multiorgan disorder. Its clinical manifestations may include facial and dental pain, facial nerve palsy, headache, temporomandibular joint pain, and masticatory muscle pain. The effects precipitated when performing dental procedures on a patient with Lyme disease must also be considered. This study discusses the epidemiology and diagnosis of Lyme disease, its prevention, and factors to consider when making a differential diagnosis. Dental care of the patient with Lyme disease and currently available treatments also are considered. Three case reports are presented.