We examined a nonplatinum-based doublet chemotherapy regimen, pemetrexed and gemcitabine given on a biweekly (every 14 days) schedule, in patients older than 70 years with newly diagnosed advanced non-small cell lung cancer. The study was closed after nine patients were treated due to excess toxicity, primarily fatigue, and nonneutropenic infection. No responses were observed. Eight of the nine patients were hospitalized during therapy and seven discontinued treatment for reasons other than progressive disease. Median progression-free survival was 1.7 months, and median overall survival was 3.9 months. We found that biweekly pemetrexed and gemcitabine was too toxic in our cohort of elderly patients with newly diagnosed advanced non-small cell lung cancer.