Ifosfamide is a cyclophosphamide analogue synthesized in the 1960s with antineoplastic activity demonstrated in early broad-ranging phase I studies conducted in Germany in the 1970s. Because of significant urothelial toxicity, phase II studies in ovarian cancer in this country were delayed until the urinary epithelial protector mesna became available in 1985. Since that time, two well-executed prospective trials have shown that this agent produces measurable responses in about 20% of women with ovarian epithelial cancer recurring after primary chemotherapy and in 12% of those with tumors refractory to first-line therapy with regimens including cisplatin. Toxicity includes moderate to severe hematologic toxicity, renal dysfunction which is usually reversible, and CNS abnormalities including lethargy, somnolence, and disorientation. The risk of toxicity may be increased in patients with compromised hepatic or renal function and in those with hydronephrosis or hypoalbuminemia.