Paraneoplastic neurologic syndromes (PNS) comprise an extensive group of heterogeneous disorders that can affect any part of the central and peripheral nervous system. There is evidence that many of these disorders are mediated by immunologic responses triggered by the presence of a cancer. Several immunologic mechanisms and many antigenic targets have been related to these disorders. Some disorders of the neuromuscular junction or peripheral nervous system are directly mediated by antibodies, and they may have a paraneoplastic origin or develop without a tumor association. For these disorders and a few PNS of the central nervous system, immunotherapy may result in neurologic improvement. However, for most PNS of the peripheral and central nervous system the response to any type of therapy is, in general, disappointing. The main concern of the clinician should be to rule out other diagnostic entities and to uncover the presence of the associated neoplasm that often remains elusive to detection. In general, the best approach to treat PNS is to discover and treat the tumor promptly, and provide supportive care for the neurologic deficits with symptomatic treatment and physical therapy. In a few cases, depending on the syndrome and if the patient is in the early stages of the neurologic disease, treatment with immunosuppression may have some effect on the PNS.