Chronic fatigue syndrome (CFS) is defined by a profound, debilitating fatigue, lasting for at least 6 months and resulting in a substantial reduction of occupational, personal, social and educational status. CFS is a relatively poorly recognized clinical entity, although everyday experience shows that there are many patients with CFS symptoms. The incidence and prevalence of CFS remain unknown in most countries; however, the working population is most affected with predominantly female patients in generative period. Although, CFS was first mentioned four centuries ago, mysterious aethiopathogensis of CFS still intrigues scientists as hundreds of studies are still published every year on the subject. About 80 different aetiological CFS factors are mentioned, which can be classified into five basic groups: genetics, immunology, infectious diseases, endocrinology and neuropsychiatry-psychology. Even today the condition is passed established based on the diagnosis by exclusion of organic and psychiatric disorders, which demands a multidisciplinary approach. As the syndrome is often misdiagnosed and mistreated, self-medication is not uncommon in CFS patients’. In addition, such patients usually suffer for years tolerating severe fatigue. Thus, at the moment there are three priorities regarding CFS; understanding pathogenesis, development of diagnostic tests and creating efficient treatment program.