Lyme disease is an infectious vector borne disease caused by a spirochete of the genus Borrelia and is transmitted by the Ixodes ticks (hard ticks). Lyme disease was first described in 1975 in a group of children living in Lyme, Connecticut in the United States of America who presented with inflammatory arthropathy that mimicked juvenile rheumatoid arthritis. Lyme disease is endemic in forested areas of the Northern Hemisphere’s temperate regions—in particular North America, Europe and Asia. This chapter covers the transmission and immunopathogenesis, demographics, clinical characteristics, diagnosis, and treatment. The diagnosis of Lyme disease is primarily clinical supported by laboratory findings. It is suspected in a patient with a history of tick bite and with a skin rash. The current recommendation for adults is 2–3 weeks of treatment with oral doxycycline 100 mg twice a day, or amoxicillin 500 mg thrice a day or cefuroxime 500 mg twice a day (in case of penicillin allergy).