Tick-borne infections occur worldwide and have been well known for more than 100 years. Some tick-borne diseases are very common while others are extremely rare. Modern molecular genetic techniques (and the wider availability of polymerase chain reaction) have lead to the discovery and classification of new pathogenic agents, especially for the order of Rickettsiales. This review deals with viral, bacterial and protozoal agents that may cause human disease. Most tick bites, and hence the tick-borne diseases, occur during the warmer time of the year. With respect to the natural reservoirs, there is a strong geographic variation among different tick-borne diseases. The history of a tick bite is not always reliable, because a tick bite may go unnoticed. The most common diseases are Lyme borreliosis and tick-borne encephalitis due to a flavivirus. The viral infections more often have neurologic signs of encephalitis, while the rikettsial infections are characterized by fever (biphasic), systemic symptoms of infection and often a rash with petechiae. Some of the tick-borne diseases are preventable by immunization, such as tick-borne encephalitis. The non-viral infections should be treated early with antibiotics, mostly following clinical suspicion, to achieve a satisfactory outcome. Either due to the virulence of the pathogen, non-utilization of preventive measures or due to delayed diagnosis and treatment, mortality rates may vary, but the tick-borne infections still cost lives.