For several decades, cancer has been a leading cause of death in Japan, with the incidence of colorectal cancer (CRC) markedly increasing due to the widespread adoption of Westernized dietary habits. Cancer prevention strategies are broadly classified into three stages: primary prevention (prevention of cancer onset), secondary prevention (early detection and treatment), and tertiary prevention (prevention of recurrence). Among these, chemoprevention utilizing food-derived compounds has gained considerable attention. Food-based chemoprevention aims to regulate or inhibit the multistep process of carcinogenesis through long-term intake of naturally derived substances. In CRC, premalignant lesions such as aberrant crypt foci (ACFs) and adenomas serve as primary targets. Numerous preclinical studies using animal models have identified a variety of compounds that suppress carcinogenesis by inhibiting cell proliferation and inducing apoptosis. Recently, efficient carcinogenesis models reflecting the influence of promoting environmental factors such as inflammation and obesity have been developed. These models allow for the evaluation not only of direct effects on cancer cells but also of modulatory actions on the carcinogenesis steps. This manuscript discusses the history of cancer prevention research and highlights emerging targets for chemoprevention.