Chronic fatigue syndrome (CFS) remains a medically unexplained syndrome, with differing aetiological models, case definitions and treatment recommendations (Ranjith, 2005:13). Sharpe & Wessely (1997:179) state that the current case definition for CFS has assumed acceptance as representing nothing more than a working definition of a clinical problem, pending further understanding. CFS has subsequently become the focus of much research and debate (Wessely, Hotopf & Sharpe, 1999:13). Notwithstanding, the definition in terms of diagnostic criteria is adequate in meeting the needs of research studies (Rutherford, 2003). Anecdotal reports, espousing the effectiveness of homoeopathic treatment of CFS, points to the use of the similimum. (Bailey, 1995:189; De Schepper, 2001:6-7; Hardy, 2005:8-10). However, the limited research available on the subject suggests that more research needs to be conducted in this regard (Wessely, Hotopf & Sharpe, 1999:371; Walach, 2004:210-211). This double-blind placebo-controlled study was conducted to determine the effectiveness of homoeopathic similimum treatment in chronic fatigue syndrome (CFS).