Chronic fatigue syndrome (CFS) is not a new disease. Similar morbidities have been known as different names since past several centuries. For example, neurasthenia, epidemic neuromyasthenia, myalgic encephalomyelitis, Akureyri disease, Royal Free disease, chronic EBV disease, post-viral fatigue syndrome etc. Much of the recent interest in CFS was generated by incidence of infection-like outbreak at Lake Tahoe in Nevada. The Center for Disease Control (USA) realized that correlation was poor between those patients who had virologic evidence of EBV infection and those who had the symptoms of chronic fatigue. This is a review of the history of CFS. (1) Historical perspectives in chronic fatigue cases in past old period, (2) Post-viral infectious fatigue and chronic fatigue (myalgic encephalomyelitis), (3) Recent trend of CFS studies and its clinical similar situation. Finally, I would like to state that we intend to draw up a new diagnostic guideline for CFS in Japan.