Ticks are obligate, blood-sucking ectoparasites that are the most common agents of vector-borne infectious disease in the United States and European countries. Ticks play an important role in transmitting several infectious agents, such as viruses, bacteria, spirochetes, rickettsia, and parasites, and tick bites cause a variety of acute and chronic infectious diseases, including Lyme disease, tick-borne relapsing fever, Rocky Mountain and Mediterranean spotted fevers, ehrlichiosis, Q fever, tularemia, babesiosis, and tick-borne viral encephalitis. Since its identification nearly 30 years ago, Lyme disease has continued to spread, and it is now the most commonly reported arthropod-borne illness in American and European countries. Rickettsial infections are widely distributed throughout the world and have a remarkable influence on public health and military activities as a possible biological weapon. Tick-borne encephalitis virus is endemic in central, eastern and northern Europe and may cause a wide spectrum of clinical forms, ranging from asymptomatic infection to severe meningo-encephalitis. This article reviews the epidemiology, microbiology, clinical manifestation, diagnosis and treatment of the major tick-borne infectious diseases in the United States and Europe.