Vavovagal syncope (VVS) is not generally associated with cardiovascular, neurological or other diseases, and, therefore, represents an isolated manifestation. Isolated VVS cannot be regarded as a disease for several reasons: spontaneous syncope occurs in about half of individuals during their lives, and the unidentified neural pathways involved in the vasovagal response are probably present in all healthy humans, with individual differences in susceptibility; VVS is induced during tilt testing in several subjects with no history of syncope; during haemorrhagic shock, the vasovagal reaction can be observed in subjects with no history of syncope; about 20% of astronauts, who are selected on the basis of their great resistance to orthostatic stress, experience syncope or presyncope on landing after a short-duration space flight; to date, no genetic basis of VVS has been demonstrated; subjects with VVS are generally normotensive and, importantly, have normal blood pressure regulation apart from the episodes of syncope; hormonal disorders or a generalized state of autonomic involvement, although frequently investigated, have never been clearly demonstrated. Isolated VVS should be distinguished from those forms that start in old age and which are often associated with cardiovascular or neurological disorders, and other dysautonomic disturbances such as carotid sinus hypersensitivity, post-prandial hypotension, and symptoms of autonomic dysfunction. In these subjects, VVS appears as an expression of a pathological process, i.e. a disease, mainly related to a generalized involvement of the autonomic nervous system, which is not yet well-defined from a nosological point of view.