If a person suffers a tick bite in tick-borne encephalitis (TBE) endemic areas, there is uncertainty on post-exposure treatment of naïve (non-immune) persons in order to protect the patient against TBE. Particularly, there are no distinct positions on the use of TBE active immunization as post-exposure treatment. Of special concern is the possibility of antibody-dependent enhancement of infection and exacerbation of disease in case of post-exposure vaccination. Such phenomena have been reported for other flavivirus infections. In the past, immune globulin treatment was recommended, but these preparations are no longer available. Active immunization by using the current immunization schedules after a tick bite will not result in appropriate neutralizing antibody concentrations within due time. Based on the assumptions that vaccination is not quick acting enough after a tick bite and that the theoretical risk of antibody-dependent enhancement cannot be excluded, no vaccination or other specific measure is currently recommended after a tick bite in non-vaccinated patients, leaving the patient in a completely dissatisfactory position. A risk/benefit analysis has been re-assessed for persons with a history with at least one vaccine injection, certain patient groups and in relation to the vaccination schedule which has been used and to the geographic area where the tick bite has occurred. In order to evaluate the value of the vaccine for post-exposure immunization, new immunization schedules have to be evaluated with respect to their capacity to induce antibodies more quickly.