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The etiology of functional somatic syndromes or disorders (FSDs) is generally considered to be a multifactorial interplay between psychological, biological, and social factors. One of the most investigated biological factors is stress responsive system dysfunction. Despite more than twenty years of research of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, however, it is yet unknown whether dysfunctions in these systems play a causal role in the etiology of FSDs and whether they are generic or FSD-specific. In this review, we will give an overview of available evidence on whether or not alterations in these stress responsive systems can be considered causal risk factors of FSDs. We conclude that although not necessary factors for FSDs in general, lowered cardiac vagal activity and hypocortisolism may be pivotal in the etiology and treatment strategy in subgroups of subjects with a FSD. Such subgroups need to be better identified.