Over the past 2 years, new insights into mutator and stromal epithelial cell interactions have enhanced the understanding of the carcinogenesis process and have identified potential new approaches to chemoprevention in diverse epithelial sites. Data testing the efficacy of chemopreventive agents in genetically mutated animal carcinogenesis models as screening tools for chemopreventive agents remain immature and point to a continued need for chemical carcinogenesis models to screen for the potential efficacy of chemopreventive agents. The Breast Cancer Prevention Trial is a published, risk-reduction trial that demonstrated a tamoxifen-induced reduction of the risk for breast cancer and focused attention on the clinical use of chemopreventive agents in healthy women. This trial highlighted the potential chemopreventive activity of selective estrogen-receptor antagonists as chemopreventives for breast cancer. New data from animal and human models continue to support the development of nonsteroidal anti-inflammatory agents as chemopreventives for colorectal cancer. Micronutrient-and diet-intervention trials for colorectal chemoprevention present a mixed picture. Although calcium and vitamin supplements, including folate, reduce the recurrence of adenomatous polyps in humans, the effect is small. Fiber supplementation does not reduce the incidence of polyps or colorectal cancer. New approaches for the chemoprevention of esophageal adenocarcinomas, hepatomas, and squamous cell skin cancers represent promising new approaches to the chemoprevention of epithelial cancers.