Topotecan is an established therapy for the treatment of recurrent ovarian cancer and has demonstrated significant antitumor activity in both platinum-sensitive and platinum-resistant patient populations. The main toxicity associated with topotecan when used in the standard 5-day dosing schedule is myelosuppression, which is generally predictable, reversible, noncumulative, and manageable. Comparative trials have shown that topotecan is as effective as paclitaxel and pegylated liposomal doxorubicin in achieving tumor response, disease stabilization, and improved overall survival. Follow-up data extending to 4 years indicate that the survival benefit persists in long-term therapy without cumulative toxic effects. There appears to be little cross-resistance between topotecan and paclitaxel, indicating that the use of concurrent or sequential combination therapy could be a valuable option. Encouraging preliminary data suggest that alternative dosing schedules may improve the therapeutic index of topotecan and that topotecan may also be active as first-line therapy in combination with taxanes and/or platinum agents. Optimization of the use of topotecan may offer potential opportunities for further improving the management of ovarian cancer.