Radiotherapy is a critical component of multi-modality treatment of LS-SCLC and has an emerging role in ES-SCLC. Many of the recent advances in the management of SCLC have come by refining the role of radiotherapy in this disease. A significant amount of research is currently focused on the targeting of specific signaling cascades implicated in SCLC pathogenesis (eg Hedgehog, c-MET, insulin-like growth factor receptor 1 [IGFR-1R], mammalian target of rapamycin [mTOR], vascular endothelial growth factor [VEGF], and p53 and Bcl-2 pathways) and on other novel approaches to therapy including treatment with a novel oncolytic virus with tropism for neuroendocrine cells and CD56-targeted drug delivery. Clinical investigations of many of these therapies are ongoing, and the results may become available over the next several years.