Small cell lung cancer (SCLC) is one of the four major histological types of lung cancer. The incidence of SCLC in developed countries has declined in recent years, presumably because of changes in cigarette composition. In the United States, SCLC is estimated to represent approximately 16% of new lung cancer diagnoses, which equates to approximately 35,000 new cases annually. In underdeveloped countries the percentage of SCLC cases may be higher. SCLC presents with a very large number of genetic alterations, including alterations of tumor suppressor genes, and copy number gains and other somatic mutations in transcription factors, enzymes involved in chromatin modification, and receptor tyrosine kinases and their downstream signaling components. 1 SCLC has a high propensity for early spread and a high initial responsiveness to cytotoxic chemotherapy that is usually followed by rapid development of resistance. Thus, essentially all patients in any stage receive a doublet combination of etoposide with cisplatin or carboplatin. For the rare patient without nodal involvement, the chemotherapy may follow surgery, and for the patient with nodal disease without distant metastases, a combination of chemotherapy with chest radiotherapy is usually given concurrently. Unfortunately, the duration of effect of these therapies is short and they are not curative in most instances, with 5-year survival rates less than 7%. No major treatment advances have occurred over the past 30 years. 2 Since the approval of topotecan in 1996, the US Food and Drug Administration (FDA) has not approved any new drugs for the treatment of patients with SCLC. 3 For these reasons SCLC was declared a “recalcitrant” cancer in the United States. However, considerable therapeutic opportunities, including targeted therapies, exist because of recent developments in understanding of the biology and molecular biology of SCLC that are in part due to the new model systems.