Cancer chemoprevention is the use of specific natural or synthetic substances with the objective of reversing, suppressing, or preventing carcinogenic progression to invasive cancer Currently, numerous chemopreventive agents are in various stages of development and testing. Part I of this two-part series provides an overview of issues unique to chemoprevention trials, including the use of surrogate biomarkers as endpoints. This is followed by a discussion of the retinoids, such as all-trans-retinoic acid (ATRA [Vesanoid]), 9-cis-retinoic acid (9cRA), and isotretinoin (Accutane), and the carotenoids (eg, beta-carotene and lycopene) and other "classic" antioxidants (eg, vitamins E and C and selenium), Research oil these agents will be delineated by disease site when applicable. Part 2, which will appear in next month's issue, will focus on hormonally mediated chemopreventive agents, such as tamoxifen (Nolvadex), finasteride (Proscar), oral contraceptives, and dehydroepiandrosterone (DHEA). Part 2 also will cover nonantioxidant natural agents, such as calcium, the polyphenols, the isothiocyanates, and genistein; nonsteroidal anti-inflammatory drugs (NSAIDS), such as celecoxib, sulindac sulfone, and aspirin; difluromethylornithine (DFMO [Eflornithine]); oltipraz; and N-acetylcysteine.