BACKGROUND: Fatigue can be the presenting complaint of a variety somatic, psychiatric and psychosomatic diseases. According to current literature, fatigue is one of the most common presenting complain in general practice. Cognitive impairment, pain and sleep dysfunction are not specific symptoms and pose a challenge due to the extensive differential diagnosis. CFS/ME, fibromyalgia and depression are all common diseases in the general population, with overlapping symptom complexes and no objective test to confirm the diagnosis. Some claim that they are variants of the same illness, with a common pathogenesis. Primary care physicians struggle with the diagnostic labeling, due to unclear symptoms in the absence of distinct diagnostic. Many general practitioners are reluctant to give a patient the CFS/ME-diagnosis because no clear management algorithm is available. Some claim that diagnosing promotes pessimistic illness perception, with non-recovery, becoming a self-fulfilling prophecy. Advantage of finding diagnosis is therefore a controversial topic. METHODS: I have used publications from Helsedirektoratet and reports from Nasjonalt Kunnskapsenter for helsetjenesten, and websites from Helsedirektoratet medisinske kodeverk ICD-10, Folkehelseinstituttet, World Health Organization, BestPractise and UpToDate. My search have been on research on the classification, diagnosis and symptom description of CFS/ME, fibromyalgia and depression. RESULTS: Although many symptoms are overlapping and not characteristic for a single disease, there are still some symptoms that can be differentiated, such as the post-exertional malaise and the extreme fatigue of CFS/ME patients, pain of fibromyalgia and self-blame, low self-esteem and the sense of guilt among of depression. CONCLUSION: Some patients show a distinct clinical presentation and can easily be distinguished from other conditions. Others are in a grey zone , where several diagnoses are possible. Whether we are dealing with three distinct conditions or not, as determined solely by symptoms, is difficult to say. Whether or not to give a diagnosis is up to the clinician and must be decided on a case by case basis.