Lyme disease (LD) is the most common tick-borne disease in the US. The overall trend has been an average annual increase in cases since surveillance was initiated by the Centers for Disease Control and Prevention in 1982. To date, 10 different Borrelia species have been described within the Borrelia burgdorferi sensu lato complex, although only Borrelia burgdorferi sensu strico, Borrelia garinii, and Borrelia afzelii have been associated with human disease. Ixodes ticks often carry more than one potential pathogen, and co-infection with B. burgdorferi and other organisms have been reported. Recent findings suggested that maintenance cycles of other tick-borne pathogens may be different than those for B. burgdorferi. A better understanding of the pathogenesis of Lyme arthritis has provided clues about the mechanisms responsible for variation in clinical expression of the disease. Results of therapeutic trials in Lyme neuroborreliosis are likely to have an impact upon treatment recommendations. A long term follow-up study of children treated for LD indicated that the prognosis is excellent in most cases. A safe vaccine for the prevention of LD has been approved in adults. Preliminary data suggested that the vaccine is safe and immunogenic in children.