Paraneoplastic neurological syndromes (PNS) are remote effects of cancer that may involve any part of the nervous system. Rarity hinders their diagnosis and management and at least 60% of cases do not present a tumor at neurological symptoms onset. An important diagnostic element is detection, in patients serum or cerebrospinal fluid, of onconeuronal antibodies which recognize antigens expressed by the nervous system and by neoplastic cells during dedifferentiation. Their detection also implies that PNS have autoimmune origin and that immunomodulation could be an effective treatment. The lack of clinical trials due to the rarity of PNS makes it hard to test the efficacy of immunomodulatory therapy, but dividing the diseases into two groups permits preliminary analysis. A humoral immunoresponse prevails in group one and antibodies seem to have a pathogenetic role, indicating antibody removal strategies. Group two are mainly PNS of the central nervous system with autoantibodies directed against intracellular antigens, probably involving a cell-mediated mechanism. Immunotherapy with steroids or cytotoxic immunosuppressive agents may be useful here. Immunomodulatory treatment is always indicated when a tumor is not found but neurological symptoms are progressing, since first line treatment is tumor identification and, where possible, removal.