Lung cancer is the leading cause of cancer deaths in the UK and the small cell lung cancer (SCLC) phenotype is the most aggressive form of this disease, with a high metastatic potential and the development of resistance to chemotherapy. Evidence now suggests that these features may be due to important links between the cancer cells and proteins in their local extracellular matrix (ECM). This article reviews the evidence for a chemoprotective effect of extracellular matrix in small cell lung cancer and discusses the importance of integrin-mediated signalling pathways in this setting.