Lung cancer is the leading cause of cancer-related death in North America and Europe. Approximately 75% of lung cancer is non-small cell lung cancer, and approximately 70% of these patients present with unresectable disease. In the past, these patients were treated with either palliative radiotherapy or other best supportive care measures. The survival of patients with stage IV disease was extremely poor. Median survival was between 16 and 17 weeks, and only 10% to 15% of patients were alive at 1 year. Cisplatin-based chemotherapy was the first therapy to show that survival could be improved. Randomized trials that compared best supportive care, including palliative radiotherapy, with cisplatin-based combination therapy showed modest improvement in the survival of these patients. On average, the median survival of patients improved by 10 weeks (from 16 to 26 weeks) and the 1-year survival rate improved by 10% (from 15% to 25%). These cisplatin-based therapies also relieved symptoms and improved quality of life at acceptable costs, which were sometimes less than those associated with best supportive care. More recently, a number of new chemotherapeutic agents (gemcitabine, paclitaxel, docetaxel, vinorelbine, and irinotecan) with high, single-agent activities and novel mechanisms of action have shown superior activity and improved quality of life when used in combination with conventional agents and with each other.