Abstract: Indenoisoquinolines are a class of compounds with antitumor activities. The study of indenoisoquinolines is to overcome the drawbacks of the camptothecins and to obtain compounds with better activities yet less poison. Recently, indenoisoquinolines were also found to have Top1-Tdp1 dual inhibition with a potential role in cancer prevention. This review briefly discusses the mechanism of Top1 inhibitors and the advantages of indenoisoquinolines with great emphasis on recent developments of indenoisoquinolines and their structure-activity relationships.