The conventional front-line chemotherapy strategy for advanced epithelial ovarian carcinoma has become adjuvant administration of platinum (carboplatin and cisplatin), either alone or, most often, in combination with a taxane. However, a number of active agents have been identified in phase II/III trials of second-line and salvage ovarian cancer patients that may augment this front-line strategy. One agent, topotecan, has antitumor activity comparable with paclitaxel in patients with recurrent ovarian cancer and is an established treatment in second-line or salvage settings. Additionally, its mechanism of action is different from paclitaxel and is nonoverlapping. These properties, coupled with the in vitro synergy observed in tumor models among topotecan, paclitaxel, and platinum, have provided the rationale for investigators to examine topotecan in front-line ovarian cancer therapy. A number of strategies for incorporating topotecan into front-line therapy are under active investigation, including the replacement of paclitaxel with topotecan, a triplet regimen with cisplatin or carboplatin and paclitaxel, a consolidation regimen consisting of several courses of a platinum agent and paclitaxel followed by several courses of topotecan, and a sequential doublet regimen in which patients receive platinum in every course as part of a doublet with alternating or sequential topotecan and paclitaxel. Preliminary data from ongoing clinical trials of these new regimens show favorable response rates and generally manageable toxicity profiles. This review summarizes the preliminary clinical findings associated with the four strategies and outlines ongoing and future randomized studies of topotecan in front-line ovarian cancer.