Chronic Fatigue Syndrome, also referred to as Myalgic Encephalomyelitis (CFS/ME) is receiving greater public health attention as a complex condition that results in substantial functional impairment. It is largely characterised by severe, medically unexplained fatigue and is associated with a broad range of further symptoms. Diagnosis remains a particular challenge and case definitions remain the primary tool in the absence of reliable and consistent clinical and biological markers. Several case definitions have been proposed and these differ significantly in symptom criteria, comorbid considerations and exclusion of other conditions, thus representing contrasting clinical profiles. This contributes to large differences in reported population, clinical, and laboratory findings reported for CFS/ME. A systematic review of worldwide prevalence studies was performed and demonstrated that the Fukuda et al. definition has been adopted as a standard. Furthermore, no studies had adopted the more recently proposed International definition. Despite the numerous studies demonstrating the public health impact of CFS/ME abroad, only one report was found estimating CFS/ME prevalence in the Australian population but this report predated the Fukuda and more recent case definitions. In the absence of a prevalence estimate for Australia, a meta-analysis was performed to pool worldwide prevalence figures of Fukuda defined cases. The pooled prevalence for self-reporting assessment was 3.28% (95% CI: 2.24–4.33) and 0.76% (95% CI: 0.23–1.29) for clinical assessment.