The response to salvage treatment in recurrent epithelial ovarian cancer (REOC), is influenced by many biologic features which should be taken into account in the process of therapeutic decision. Until recently, single agents have been considered effective as combination chemotherapy in REOC and they still represent an option for well-defined categories of patients. In clinical practice, the selection of drugs for second-line treatment can be based on the knowledge that tumor size and response to prior platinum are predictors of response and that the efficacy of some commonly used single agents is supported by well designed clinical studies. Only two single-agent randomized studies with long-term survival analyses have been published; in the topotecan versus paclitaxel study, performed on a total of 235 patients, the long-term survival results did not confirm the initial report of a superiority of topotecan, with a median survival of 63 weeks and 53 weeks for patients treated with topotecan, and, respectively, paclitaxel. No comparative data were provided in the subgroup of potentially platinum-sensitive disease. In the phase III study of pegylated liposomal doxorubicin versus topotecan, into which 474 patients were treated between 1997 and 1999, the higher efficacy of pegylated liposomal doxorubicin was even more evident in the long-term survival analysis, with a 18% reduction in the risk of death, in the overall population which increased to 30% in the subset of platinum-sensitive patients. The survival after the two treatments, however, was not different in the group of patients with platinum-refractory disease. The toxicity profile of the two drugs was completely different, with palmar-plantar erythrodysestesia as most common adverse event after pegylated doxo (35% of patients) and severe neutropenia after topotecan (77% of patients). These data confirm the role of pegylated liposomal doxorubicin in the management of REOC and indicate that the identification of new active drugs in this disease is relevant but also feasible only in platinum-sensitive patients.