Three large randomized trials (GOG-104, GOG-114, GOG-172) have shown the advantage of a combination of intravenous (IV) and intraperitoneal (IP) administration of chemotherapy over IV administration alone in optimally-debulked ovarian cancer. A significant advantage of IP chemotherapy is that high concentrations of drugs can be maintained within the peritoneal cavity with less systemic toxicity than IV chemotherapy of similar doses. Two pharmacokinetic problems appear to limit the effectiveness of IP chemotherapy: poor tumor penetration by the drug and incomplete irrigation of serosal surfaces by the drug-containing solution. Combined IP/IV administration of chemotherapy may be associated with a significantly increased short-term risk of toxicity compared with IV chemotherapy. However, the toxicity is usually short-term and manageable. Substitution of carboplatin for cisplatin may reduce the toxicity of IP platinum, but the optimal IP regimen for women with optimally-debulked ovarian cancer should be determined. In conclusion, patients with optimally-debulked FIGO stage III ovarian cancer should be counseled about the clinical benefit associated with combined IV and IP administration of chemotherapy.