Many professionals have described the clinical presentation of myalgic encephalomyelitis (ME), but recent efforts have focused on the development of ME criteria that can be reliably applied. The current study compared the symptoms and functioning of individuals who met the newly-developed Institute of Medicine (IOM) clinical criteria to a revised version of the London criteria for ME. While 76% of a sample diagnosed with chronic fatigue syndrome (CFS) met the IOM criteria, 44% met the revised London criteria. The revised London criteria identified patients with greater physical impairment. The results of this study indicate the need for a standard case definition with specific guidelines for operationalization. The application of case definitions has important implications for the number of individuals identified with ME, the pattern of symptoms experienced by these individuals, and the severity of their symptoms and functional limitations. Sample heterogeneity across research studies hinders researchers from replicating findings and impedes the search for biological markers and effective treatments.