Purpose of review The management of advanced non-small cell lung cancer remains disappointing and difficult. At least 65% of patients present with either locally advanced inoperable disease (stage IIIB) or with distant metastases (stage IV disease). The average age of newly diagnosed lung cancer patients is approaching 68 years and they represent a difficult group to palliate without causing treatment-related symptoms. This article examines the current status of chemotherapy as a primary therapy and evaluates the treatments of choice in terms of efficacy, toxicity, survival, and impact on quality of life. In particular, it reviews the recommendations for chemotherapy in the elderly and for those with a poor performance status. The role of the newer growth factor-inhibiting agents is also discussed. Recent findings Chemotherapy prolongs the survival of patients with advanced non-small cell lung cancer compared with best supportive care alone by 3 to 6 months, with the newer generation of agents producing slightly better survival statistics and some improvement in quality of life. Better performance status patients always do better than those with a poor status, and they tolerate therapy better. The new growth-modifying agents do not as yet have a clear-cut role in therapy, but promise both to improve our understanding of how to inhibit tumor growth and to identify which patients may respond to these agents. Summary The treatment of advanced non-small cell lung cancer remains difficult and disappointing, New effective agents are urgently needed.