Topoisomerase I remains a target of active interest in the development new anticancer agents because topoisomerase I inhibitors are clearly active and effective anticancer drugs and because the current topoisomerase I inhibitors are molecules that can be improved upon. There are currently camptothecin and non-camptothecin topoisomerase I inhibitors in preclinical and clinical development. Each of these investigational molecules depicted in this book may have properties that lead to improved therapeutic benefits to patients in future.