Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Chronic fatigue syndrome: understanding a complex illness


Chronic fatigue syndrome (CFS) is a debilitating illness that affects many people. It has been marred by controversy, from initial scepticism in the medical community about the existence of the condition itself to continuing disagreements — mainly between some patient advocacy groups on one side, and researchers and physicians on the other — about the name for the illness, its aetiology, its pathophysiology and the effectiveness of the few currently available treatments. The role of the CNS in the disease is central in many of these discussions. Nature Reviews Neuroscience asked four scientists involved in CFS research about their views on the condition, its causes and the future of research aimed at improving our understanding of this chronic illness.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Carruthers, B. M. et al. Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. J. Chronic Fatigue Syndrome 11, 7–36 (2003).

    Article  Google Scholar 

  2. 2

    Fukuda, K. et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann. Intern. Med. 121, 953–959 (1994).

    CAS  Article  PubMed  Google Scholar 

  3. 3

    Sharpe, M. et al. A report — chronic fatigue syndrome: guidelines for research. J. R. Soc. Med. 84, 118–121 (1991).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4

    Holmes GP. et al. Chronic fatigue syndrome: a working case definition. Ann. Intern. Med. 108, 387–389 (1988).

    CAS  Article  PubMed  Google Scholar 

  5. 5

    White, P. D. et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 377, 823–836 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6

    Lombardi, V. C. et al. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 326, 585–589 (2009).

    CAS  Article  PubMed  Google Scholar 

Download references


Members of the Trans-NIH ME/CFS Research Working Group, the Office of Research on Women's Health and the Institute Offices of Communications contributed to the responses by D.M.

Author information



Corresponding authors

Correspondence to Stephen T. Holgate or Anthony L. Komaroff or Dennis Mangan or Simon Wessely.

Ethics declarations

Competing interests

S.T.H. is Chair of the UK Medical Research Council (MRC) CFS/ME Expert Group.

Related links

Related links


Centers for Disease Control and Prevention CFS homepage

UK Medical Research Council CFS/ME funding homepage

Trans-NIH ME/CFS Research Working Group

Simon Wessely's homepage

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Holgate, S., Komaroff, A., Mangan, D. et al. Chronic fatigue syndrome: understanding a complex illness. Nat Rev Neurosci 12, 539–544 (2011).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing