Topoisomerases are nuclear enzymes involved in steps of DNA metabolism which require topological modifications. Interestingly, these enzymes have been discovered to be targets of several anticancer drugs in common clinical use. Alterations of the topoisomerase enzymes have been described as associated with the development of drug resistance to topoisomerase inhibitors. The best known alterations are reduced gene expression and mutations in the genes. The present knowledge of the role of topoisomerases in lung cancer, and in small cell lung cancer in particular, is described here.