Tick bite fever has been a constant feature of the South African medical landscape. While it was recognised many years ago that there was a wide spectrum of clinical severity of infection, only recently has It been established that there are two aetiologlcal agents, with different epidemiologies and clinical presentations. Rickettsia conorii infections resemble the classical Mediterranean spotted fever (fièvre boutonneuse), and patients are sometimes at risk of severe or even fatal complications. On the other hand, African tick bite fever is a separate entity caused by Rickettsia africae and tends to be a milder illness, with less prominent rash and little tendency to progress to complicated disease. Irrespective of the agent, the treatment of choice for tick bite fever in South Africa remains doxycycline or tetracycline, and the role of macrolide and quinolone antibiotics is still unclear, or at least restricted.