Autonomic paraneoplastic neurological syndromes (PNS) typically present as chronic gastrointestinal pseudo-obstruction or orthostatic hypotension and usually occur in association with other PNS rather than in isolation. Although rare, they are often debilitating, sometimes fatal, and probably seriously underdiagnosed. Here, we discuss the clinical, immunological and oncological features of these syndromes and review the molecular and cellular mechanism that may underlie the triggering and maintenance of their autoimmune pathogenesis.