Botanicals have been used for the treatment of various human diseases throughout history. In addition, botanicals play a role in disease prevention. For example, epidemiologic studies have suggested that a reduced risk of cancer is associated with high consumption of vegetables and fruits. Thus, the cancer chemopreventive potential of naturally occurring phytochemicals is of great interest. In this review, we discuss the cancer chemopreventive activity of cruciferous vegetables such as cabbage and broccoli, Allium vegetables such as garlic and onion, green tea, Citrus fruits, tomatoes, berries, ginger and ginseng, as well as some medicinal plants. In addition, methods for the discovery of active compounds from plant sources are described. Several lead compounds, such as brassinin (from cruciferous vegetables like Chinese cabbage), sulforaphane (from broccoli) and its analog sulforamate, withanolides (from tomatillos), and resveratrol (from grapes and peanuts among other foods), are in preclinical or clinical trials for cancer chemoprevention. Phytochemicals of these types have great potential in the fight against human cancer, and a variety of delivery methods are available as a result of their occurrence in nature.