Although non-small cell lung cancer has long been considered poorly responsive to chemotherapy, there are now a number of chemotherapeutic agents with reproducible activity in this disease, including cisplatin and ifosfamide. Another agent, etoposide, has been rationally incorporated into combination regimens for this disease based on demonstrated preclinical synergy. We review recent studies combining these three agents in the treatment of metastatic non-small cell lung cancer as well as prospects for further development.