Oxidative stress is now recognized as an important etiological factor in the causation of several chronic diseases including cancer, cardiovascular diseases, osteoporosis, and diabetes. Antioxidants play an important role in mitigating the damaging effects of oxidative stress on cells. Lycopene, a carotenoid antioxidant, has received considerable scientific interest in recent years. Epidemiological, tissue culture, and animal studies provide convincing evidence supporting the role of lycopene in the prevention of chronic diseases. Human intervention studies are now being conducted to validate epidemiological observations and to understand the mechanisms of action of lycopene in disease prevention. To obtain a better understanding of the role of lycopene in human health, this chapter reviews the most recent information pertaining to its chemistry, bioavailability, metabolism, role in the prevention of prostate cancer and cancer of other target organs, its role in cardiovascular diseases, osteoporosis, hypertension, and male infertility. A discussion of the most relevant molecular markers of cancer is also included as a guide to future researchers in this area. The chapter concludes by reviewing global intake levels of lycopene, suggested levels of intake, and future research directions.