Lyme borreliosis is the most common human tick-borne illness in the Northern Hemisphere. The causative agent is the spirochete Borrelia burgdorferi species complex, and the hard-shell ticks of the genus Ixodes is responsible for pathogen transmission from animals to humans. The incidence of the disease is increasing year by year and although lyme disease is not fatal, it can affect the skin, heart, nervous, and musculoskeletal system with an impairment of quality of life. The appropriate diagnosis of lyme disease should be promptly treated by antibiotics to prevent late stage of the disease. The choice of antibiotics depends on many factors such as the stage of the disease, the drug efficacy, adverse effects, type of delivery, duration of treatment, and cost. Treatment failure occurs as a result of many reasons, re-infection is possible. The recommended treatment schedule in the Czech Republic is presented.