A characteristic feature of fenretinide is the ability to inhibit cell growth through the induction of apoptosis with mechanisms that may be both receptor-dependent and receptor-independent. Chemopreventive efficacy of fenretinide has been investigated in clinical trials targeted at different organs. Results of a phase III secondary prevention trial suggest a benefit in preventing second breast malignancies in premenopausal women with early breast cancer. A potential benefit of fenretinide with ovarian cancer and a reduction of new occurrences of leukoplakia have also been observed in clinical trials with this agent. However, no effects on DNA content of urothelial cells from bladder washings and on recurrence rate were noted in a study of patients with superficial bladder tumors. Future trials using surrogate biomarkers may aid in rapid evaluation of the chemopreventive activity of fenretinide with various targeted organs.