Because treatment options for advanced metastasized cancers remain inadequate, developing effective approaches for the prevention of cancer has become an important goal to reduce cancer burden. One such strategy is through chemoprevention, preferably by the use of non-toxic dietary substances and botanical products. Pomegranate, used for centuries for its medicinal properties is now being recognized as a potential chemopreventive and anticancer agent. Increasing body of evidence has underscored the cancer preventive efficacy of pomegranate both in vitro and in vivo animal models. The emerging data provide new insights into the molecular framework needed to establish novel mechanism-based chemopreventive strategies for various human cancers.