The literature concerning the use of anthracyclines in the treatment of non-small cell lung cancer (NSCLC) is reviewed here. Overall, the activity of doxorubicin (DOXO) is unsatisfactory, whereas, the analogous epidoxorubicin (EPI) yields a 30% response rate (RR) when administered at intermediate-high doses. All active drugs, including EPI, should be considered to design the most active combination. Mainly, in the setting, in which an objective response is very important, for instance the neo-adjuvant pre-operatory setting.