Eastern Cooperative Oncology Group (ECOG) investigators have tested a variety of single-agent and combination regimens in patients with non-small cell lung cancer (NSCLC) during the last 2 decades. The following observations have been made. (1) The mitomycin/vinblastine/cisplatin regimen produced a trend for higher response rates in two studies and a significantly higher response rate in a third study. Survival, however, tended to be shorter in patients receiving this regimen. (2) Carboplatin produced a 9% overall response rate and a median survival of 31.7 weeks, which was slightly but significantly longer than the median survivals obtained with three combination chemotherapy regimens. (3) Paclitaxel produced an overall response rate of 21% and a 1-year survival rate of 40% in previously untreated NSCLC patients. This observation led to a phase III trial in which paclitaxel (135 mg/m2 and 250 mg/m2) was combined with cisplatin and compared with etoposide/cisplatin. Response rates for each of the paclitaxel/cisplatin regimens (26% for 135 mg/m2 paclitaxel and 31% for 250 mg/m2) were significantly higher than the response rate for etoposide/cisplatin (12%), but response between the two paclitaxel/cisplatin arms was not significantly different. At this point, there is a trend toward longer survival in each of the paclitaxel/cisplatin arms, but the final survival analyses have not been completed. In the next phase III trial, ECOG will evaluate paclitaxel (135 mg/m2) plus cisplatin in comparison to three other regimens—docetaxel/cisplatin, gemcitabine/cisplatin, and carboplatin/paclitaxel.