Although the incidence of small cell lung cancer (SCLC) has declined during the past 30 years, it remains a significant cause of cancer mortality in the United States and across the world. With appropriate treatment, about 20% of patients who present with limited stage SCLC can be cured of their disease. Unfortunately, the outcome for the remainder of patients is extremely poor. The only significant advance in extensive stage SCLC in the past 2 decades is the recent discovery that prophylactic cranial irradiation improves survival in those patients whose disease has responded to initial chemotherapy. Numerous attempts to enhance the antitumor effects of traditional chemotherapy for SCLC have not been successful. As the understanding of the biology of SCLC increased, a number of rational molecular targets for therapy have been identified. Although initial attempts at "targeted therapy" in SCLC have been unsuccessful, several newly identified targets hold promise and give hope that significant improvements in therapy for this challenging disease are not far away.