For more than 25 years, chemotherapy has been the cornerstone of treatment for small-cell lung cancer. Many studies have tested a wide variety of drugs in different combinations, resulting in a number of standard combination chemotherapy options. Radiotherapy to the primary tumor, after having been out of favor for a time, is now considered an element of standard therapy for patients with limited disease, although a number of questions remain concerning its optimal use. Because the overall outcome of therapy for small-cell lung cancer is not at all satisfying, further research is needed to find a better use of old and new drugs. This article provides a historic overview of therapy for small-cell lung cancer, followed by examples of emerging concepts and current research in such areas as dose escalation, second-line therapy, and new drugs. Selection of optimal first-line therapy for the individual patients is also discussed, based on disease stage, performance status, and other considerations.