Chemopreventive agents must be administered on a long-term basis to healthy individuals; hence, emphasis must be placed not only on efficacy but also on a high level of safety. In addition, cancers develop through a multistep process in which molecular and biochemical alterations accumulate in target cells over long periods of time, the end result of which is a clinically apparent malignancy. Development of effective chemopreventive agents, or combinations of agents requires identification of the points in this process in which intervention with a pharmacologic agent or changes in diet through consumption of natural botanicals or modification of diet-related components could inhibit, reverse and/or delay development of invasive and/or metastatic cancers and a knowledge of their mechanisms of action.