Oxidative stress is now recognized as an important etiological factor in the causation of several chronic human diseases, including cancer, cardiovascular diseases, osteoporosis, and diabetes. More recently, it has also been associated with other diseases that include but are not limited to respiratory diseases, hypertension, male infertility, skin diseases, and neurodegerative diseases. Antioxidants have the ability to mitigate the damaging effects of oxidative stress and thereby lower the risk of human diseases. Among the antioxidants, vitamins such as A, C, and E and biologically active phytochemicals present in our food such as carotenoids and polyphenols have been investigated over the past several decades. Lycopene, a potent antioxidant, is one of the major carotenoids present in foods. Although it is present in many fruits and vegetables, tomatoes and tomato products are the major sources in human diet. The initial interest in lycopene as a beneficial antioxidant against human diseases was due to its role in prostate cancer. This interest was then expanded to other cancers and CVD. More recently, scientific research is being directed at its role in other human diseases. This chapter reviews the most recent information pertaining to some of these other human diseases. However, it is important to note that the role of lycopene is not limited to the diseases reviewed here. Further human intervention studies with well-defined and larger numbers of participants, the use of recently published end-point measurements, and the use of physiologically relevant doses of lycopene are needed to confirm its positive role and the most effective dose levels. Based on such observations, health and dietary guidelines can be formulated to help health professionals in the prevention, management, and treatment of human health disorders.