Since the discovery of the Lyme disease spirochete in North America in 1982 and in Europe in 1983, a plethora of studies on this unique group of spirochetes that comprise Borrelia burgdorferi sensu lato has been accumulated. In an attempt to compare and contrast Lyme borreliosis in Europe and North America we have reviewed the biology of the aetiologic agents, as well as the clinical aspects, diagnosis and treatment of this disease on both continents. Moreover, we have detailed the ecology of the Ixodes ticks that transmit this infection and the reservoir hosts that maintain the spirochete cycle in nature. Finally, we have examined the transmission dynamics of the spirochete on both continents, as well as the available prevention strategies. Although it has been over two decades since the discovery of the Lyme disease spirochete, Lyme borreliosis is an expanding public health problem that has defied our attempts to control it. By comparing the accumulated experience of investigators in North America and Europe, where the disease is most frequently reported, we hope to advance the cause of developing novel approaches to combat Lyme borreliosis.