Although the benefits of chemotherapy have been established for treating non-small-cell lung cancer (NSCLC), several clinical issues remain. Currently, doublets offer the maximum benefit in terms of balancing efficacy with tolerability to patients with advanced-stage disease. The optimal duration of therapy continues to be evaluated, and several agents have emerged for treating patients with recurrent advanced NSCLC. Chemotherapy benefits for populations underrepresented in clinical trials, such as elderly patients and patients with poor performance status, also need to be established. Although combination therapy with carboplatin/paclitaxel is one regimen of choice for treating advanced NSCLC, there may be ways to optimize its delivery schedule including use of weekly administration of paclitaxel and monthly administration of carboplatin. In addition, biologic approaches are being investigated to determine if these agents may be appropriate for treating patients with advanced NSCLC and how best to administer them. In resectable stage IIIA disease, benefits of preoperative chemotherapy and chemotherapy/radiation therapy followed by surgery continue to be evaluated. Although associated with esophageal toxicity, in non-resectable stage IIIA/IIIB disease, concurrent chemotherapy/radiation therapy has emerged as the schedule of choice. Yet, benefits of higher radiation dosage need evaluation. Based on phase II studies, preoperative chemotherapy with or without radiation may benefit patients with early-stage disease, but studies have been inconclusive, yielding mixed results. Recent trials of adjuvant chemotherapy following surgical resection in early-stage NSCLC have yielded conflicting results, with some trials showing no benefit to adjuvant therapy. Trials under way will determine the future of adjuvant or induction chemotherapy in treating this patient population.