Our ability to detect and treat most primary cancers has improved dramatically given the advances in our understanding of cancer biology. However, with increased life expectancy and our inability to treat or cure advanced stages of cancers, the number of cancer-related deaths is expected to double in the next decade. Epidemiological studies suggest that dietary factors are an important aspect that influences cancer risk. Despite a lack of scientific evidence in most cases, cancer patients have whole-heartedly accepted the concept of “alternative medicine” using natural compounds and spent more than $1B a year on herbal supplements. Given the significant toxicity-associated problems with current long-term standard of care, scientifically validated natural supplements can serve as novel and effective alternative strategies for effective cancer management. We will discuss the utility of natural products in modulating critical signaling pathways for effective cancer prevention with special emphasis on prostate cancer and their potential translational benefit.