Mitomycin has proven to be among the most active drugs available for the single-agent treatment of non-small cell lung cancer (NSCLC). In combination with vinca alkaloids and cisplatin, mitomycin can produce response rates greater than or equal to 50% in properly selected patients. In our experience, such responses were achieved using moderate doses (7 or 8 mg/m2) of mitomycin, which also resulted in fewer hematologic and other toxicities. Delivery of MVP (mitomycin/vinca alkaloid/cisplatin) to 150 patients with stages III and IV NSCLC during the last decade showed maximal response was achieved after two or three cycles of therapy. A comparative analysis of results reported using MVP regimens suggests that high response rates are associated with greater dose-intensive use of cisplatin and lesser dose-intensive use of mitomycin. Although the role of MVP in the treatment of advanced NSCLC is unclear, use of mitomycin-containing regimens as part of a multidisciplinary approach to stage IIIA NSCLC has yielded high response rates and has successfully downstaged patients prior to surgery. Randomized clinical trials will be required to validate these findings, but the focus of future research should be on discovering new agents with greater activity and on developing new approaches wherein these agents can be delivered with maximum efficacy and minimum toxicity.