In summary, SCLC kills 45,000 Americans each year. The treatment of SCLC has not changed since the introduction of cisplatin and etoposide during 1970s. Research in cancer biology has identified several genetic alterations that could be of therapeutic importance. Novel agents that target these genetic alterations are currently in development. Patient selection will be key in order to determine the activity of these agents. Understanding the biology of this disease is the key to successful interventions and personalizing therapy.