Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most severe and unpredictable side effects of modern anticancer treatment. In recent years, a clear understanding of the importance of an integrated approach to CIPN has become evident, and efforts are increasing to better characterize its features and to identify more accurate methods to report and grade its occurrence. The clinically relevant impact of CIPN on cancer patients has been known for a long time, but knowledge of its pathogenetic aspects is still very limited. This incomplete knowledge is one of the major limitations in identifying targets for evidence-based neuroprotective strategies. Nevertheless, several studies have been devoted to the prevention or at least the effective treatment of symptoms secondary to peripheral nerve damage and to the early identification of patients at high risk of developing severe CIPN. Unfortunately, none of these studies has been successful and the optimal management of CIPN patients is still an unmet clinical need. Therefore, the modification of chemotherapy is currently the only available approach to limit the severity of neuropathy in the vast majority of patients. The indications for treatment modification are not universally accepted and they can differ among the various drugs. Generally, treatment modification should be considered as soon as symptoms and signs impair the daily life activities of the patient, but the possibility of a delayed worsening of CIPN after treatment withdrawal ("coasting") should always be considered, and delay of modification decisions should be avoided.