In early clinical trials, oxaliplatin has demonstrated significant activity against colorectal cancer in combination with 5-fluorouracil (5-FU) and folinic acid (FA), both in metastatic as in radically resected disease. The drug differs from the other two most important platinum compounds (cisplatin and carboplatin) for the absence of nephrotoxicity or for the reduced drug-induced ototoxicity. During its administration, two different types of neurological symptoms can be experienced: the first one occurs during or immediately after the end of the infusion and it appears as a transient peripheral sensory neuropathy manifesting as paresthesias and dysesthesia in the extremities sometimes accompanied by muscular contractions of the extremities or the jaw (triggered or enhanced by exposure to cold). The second one occurs after long-term administration of oxaliplatin presenting with deep sensory loss, sensory ataxia and functional impairment (similar to those observed with cisplatin). This type of neurotoxicity is usually late-onset and correlated with the cumulative-dose of oxaliplatin. The aim of this review is to analyse the mechanism underlying induction of neurotoxicity and the possible treatments to prevent and to treat it.