Central and peripheral nervous system toxicity are frequent complications of most chemotherapy regimens, often leading to reduction of dosages or cessation of the responsible drugs. However, sometimes the afflicted toxicity may not be reversible, especially if it is not recognized early, further compromising the quality of life of the cancer patients. The most common chemotherapeutic agents that might cause CNS toxicity manifested as encephalopathy of various severities include methotrexate, vincristine, ifosfamide, cyclosporine, fludarabine, cytarabine, 5-fluorouracil, cisplatin and the interferons (alpha > beta). Involvement of the peripheral nervous system manifested as distal peripheral neuropathy results after therapy with cisplatin, vincristine, taxanes, suramin and thalidomide. Although several compounds have been proposed as neuroprotective agents, few have been shown to be active against the chemotherapy induced neurotoxicity.