The camptothecin topoisomerase I-targeting agents are new class of antitumor drugs with demonstrated clinical activity in human malignancies, such as colorectal cancer and ovarian cancer. Currently, irinotecan and topotecan are the most widely used camptothecin analogs in clinical use and clinical trials are ongoing to better characterize their spectra of clinical activity, to determine their optimal schedules of administration and to define their use in combination with other chemotherapeutic agents. Newer camptothecin analogs in clinical development, such as 9-aminocamptothecin, 9-nitrocamptothecin, GI147211 and DX-8951f, are also being studied to determine if they have improved toxicity and efficacy profiles compared with existing analogs. Other potential clinical applications include the use of camptothecin derivatives as radiation sensitizers or as antiviral agents. The successful development of the camptothecins as antitumor agents highlights the importance of topoisomerase I as a target for cancer chemotherapy.