Nearly 100 years ago, Afzelius described a patient with an expanding skin lesion, called erythema migrans, which is now known to be the initial skin manifestation of Lyme borreliosis. Approximately 70 years later, in 1976, epidemiologic evaluation of a cluster of children with arthritis in Lyme, Connecticut led to a complete description of the infection. During the subsequent years, investigators in a number of countries have made remarkable strides in the elucidation of this tick-borne spirochetal infection. The purpose of this review is to discuss the current status of Lyme borreliosis, including areas in which knowledge of the infection is still incomplete.