The ras family of genes have been identified as potential targets for therapeutic intervention because of somatic mutations in different human cancers. They are mutated in non-small cell lung cancer (NSCLC) approximately 20% of the time. The enzyme farnesyl transferase is involved in posttranslational modification of the ras proteins by covalently linking a farnesyl group to the ras protein. This permits the ras protein to be translocated to the surface membrane, allowing the protein to be involved in signaling for increased proliferation and inhibition of apoptosis. The class of farnesyl transferase inhibitors is designed to block farnesylation and prevent the mature ras signaling and thus inhibit cell proliferation and facilitate apoptosis. Multiple agents that inhibit farnesylation have been developed, and two farnesyl transferase inhibitors have been tested in patients with lung cancer in three Phase II trials. R115777 has been studied in patients with NSCLC and in patients with relapsed small cell lung cancer (SCLC) after chemotherapy. There has been a single trial of L-778,123 in patients with untreated NSCLC. No objective tumor responses in patients with stage IIIB/IV NSCLC were seen in these studies. There were also no objective responses among the 22 patients with relapsed SCLC treated with R115777. The median survival for the 44 patients with NSCLC treated with R115777 was approximately 8 months, whereas it was 11 months for the 23 patients treated with L-778,123. R115777 and L-778,123 were well tolerated in these studies but showed no significant activity as single-agent therapy in relapsed SCLC or untreated NSLC.