People 80 years of age and older constitute 17.8% of all lung cancer patients in the United States. Because the life expectancies of 80-year-old men and women are 87.3 years and 89.0 years, respectively, non-small cell lung cancer shortens lives in addition to causing morbidity. In this retrospective study, all patients with chemotherapy-naive advanced non-small cell lung cancer 80 years of age and older treated at the M. D. Anderson Cancer Center with one or more follow-ups were identified from the database for the years 1997 to 2004. A cohort of patients younger than 80 years old was matched based on treatment year, race, histology, and gender in a 2:1 ratio. Of 13,690 thoracic oncology patients, 496 (3.6%) were 80 years of age and older, of whom 46 met the criteria. In older and younger patients, respectively, platinum doublets were given in 43% versus 79% (p < 0.0001), the response rate was 41% versus 47%, the median progression-free survival was 5.55 versus 3.91 months (p = 0.216), and the median overall survival was 10.7 versus 9.8 months (p = 0.43). Hematologic and nonhematologic toxicities were similar. Our data indicate that selected patients 80 years of age and older may tolerate and benefit from chemotherapy, and prospective evaluation of these patients is indicated.