In writing a history of any illness there is always a dilemma whether to attempt the story of the condition ‘itself’, the medical attempts to define its nature, or to glimpse it via our changing reactions. The easiest is a straightforward account of the attempts of scientists to solve a problem—the classic medical detective story. However, this is often more fiction than fact. Medicine rarely moves smoothly from ignorance to knowledge, but often in a more circular fashion. A historical approach is thus not solely a record of who did what, but also contributes to our understanding of the problems under scrutiny in this issue. Terminology is never easy in this subject, but the following conventions will be used: The terms neurasthenia and ME will be used in their actual context (as authors themselves used them), without defining either. Post-infectious fatigue syndrome (PIFS) will cover similar conditions when related to infective episodes. All will be used in a neutral fashion, to refer to changing realities as understood by doctors and historians. This chapter attempts both chronological description and social analysis. The justification for this approach is clear in the case of neurasthenia, since ‘as so little was known of its pathological basis physicians’ statements regarding the disease were composed more of social and cultural elements than of scientific knowledge.1 Although much has changed, a contemporary account still reveals as much about cultural attitudes as the advance of science.2