• There is no diagnostic test, validated biomarker, or clear pathophysiology or curative treatment.
  • The core symptom of fatigue affects both physical and cognitive activities and features a prolonged post-activity exacerbation triggered by tasks previously achieved without difficulty.
  • Although several different diagnostic criteria are proposed, for clinical purposes only three elements are required: recognition of the typical fatigue; history and physical examination to exclude other medical or psychiatric conditions which may explain the symptoms; and a restricted set of laboratory investigations.
  • Studies of the underlying pathophysiology clearly implicate a  range of different acute infections as a trigger for onset in a significant minority of cases, but no other medical or psychological factor has been reproducibly implicated.
  • There have been numerous small case-control studies seeking to identify the biological basis of the condition. These studies have largely resolved what the condition is not: ongoing infection, im- immunological disorder, an endocrine disorder, a primary sleep disorder,  or simply attributable to a psychiatric condition.
  • A growing body of evidence suggests CFS arises from functional (non-structural) changes in the brain, but of uncertain character and location. Further functional neuroimaging studies are needed.
  • There is clear evidence for a genetic contribution to CFS from family and twin studies, suggesting that a large-scale genome-wide association study is warranted.
  • Despite the many unknowns in relation to CFS, there is significant room for improvement in the provision of diagnosis and supportive care. This may be facilitated via clinician education.