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Pomegranate (Punica granatum) has been used since ages as a folk medicine. Studies have shown that pomegranate extracts have a role in various signaling pathways involved in inflammation, cellular transformation, hyperproliferation, angiogenesis, initiation of tumorigenesis, and eventually suppressing the final steps of tumorigenesis and metastasis. In this chapter, we have discussed some of the polyphenolic constituents present in pomegranate and their medical value, and we then discussed studies on chemopreventive/chemotherapeutic properties of pomegranate against various types of cancer, such as skin, prostate, colon, head and neck and lung cancers in cell culture systems, animal models and humans.