Amifostine (WR-2721, Ethyol), a phosphorylated aminothiol, was originally developed as a radioprotective agent. Since numerous preclinical studies showed that, following dephos-phorylation to the active thiol WR-1065, amifostine selectively protected normal tissues from the damaging effects of irradiation and of several cytotoxic agents without reducing the anti-tumor activity, an intensive clinical development in chemo- and radiotherapy studies was performed. In clinical trials, amifostine proved to be an effective cytoprotector in patients receiving treatment with antineoplastic agents or irradiation. It significantly reduced the incidence and severity of acute, cumulative and delayed toxicities associated with antineoplastic therapy, allowing better patient tolerance of current regimens and possible dose escalation. This protection is achieved without any reduction in the antitumor efficacy. Thus, the integration of amifostine into oncological regimens represents a new ‘preventive’ strategy for a more tolerable and selective ther