Improvements in ovarian cancer management mean that it may now be a long-term disease for which treatment must be carefully considered. Optimal sequencing of chemotherapy may help to enhance patients' benefit of therapy and minimize toxicity. The response to retreatment with platinum or a platinum/taxane combination is strongly influenced by the treatment-free interval after initial therapy with a platinum combination. Response rates to platinum retreatment in platinum-resistant patients (relapse within 6 months) are lower than those in platinum-sensitive patients (relapse after 6 months). Increasing the platinum-free interval by using non-platinum-based chemotherapy for treatment after relapse appears to increase the likelihood of response to later rechallenge with platinum. Many alternative agents have been investigated for the treatment of patients with relapsed ovarian cancer, including single-agent topotecan, which has been shown to achieve favorable responses. Topotecan may cause myelosuppression, which is noncumulative but tends to increase in direct correlation with the number of prior chemotherapy courses. Therefore, the best use of topotecan may be early in the course of salvage therapy. The hematologic toxicities associated with topotecan can also be reduced by adjusting the dose and schedule. Prolonged use of topotecan may be feasible and potentially beneficial in some patients.