Several antineoplastic drugs induce severe toxic damage of the peripheral nervous system and chemotherapy-induced peripheral neurotoxicity (CIPN) can be dose limiting. Moreover, CIPN signs and symptoms can be permanent and severely impair the patients' quality of life even after drug withdrawal. Despite extensive investigation, the exact mechanisms of neurotoxic action at the basis of CIPN are not completely known and it is likely that they can be at least in part different from the mechanisms of antineoplastic action of the drugs. A possible instrument to investigate on this important issue is represented by the evaluation of the effect of compounds used to reduce the toxicity of antineoplastic drugs in pre-clinical and clinical settings. This review will be focused on the most clinically-relevant neurotoxic antineoplastic drugs and on the results obtained with several different classes of putative neuroprotectants.