Ginseng (Panax ginseng, C.A. Meyer) has been a popular herbal remedy used in eastern Asian cultures for thousands of years. In North America, the ginseng species indigenous to both Canada and the United States (Panax quinquefolium) represents an important industry for both domestic and export markets. There are numerous theories and claims describing the efficacy of ginseng, which can combat stress, enhance both the central and immune systems and contribute towards maintaining optimal oxidative status against certain chronic disease states and aging. Risk issues concerning the safety of ginseng at recommended dosages are less prominent and scientifically based. While some epidemiological or clinical studies have reported indications of efficacy for specific health benefits or potential toxicity, there are an equal number of studies that provide contradictory evidence. This situation has led to questionable conclusions concerning specific health benefits or risks associated with ginseng. Recent advances in the development of standardized extracts for both Panax ginseng (G-115) and Panax quinquefolius (CNT-2000) have and will continue to assist in the assessment of efficacy and safety standards for ginseng products. This paper reviews the scientific literature and evidence for ginseng efficacy and safety derived mostly from in vitro and animal studies and places emphasis on the need for more randomized, double-blinded, placebo clinical studies that can provide unequivocal conclusions. An example of the efficacy and safety of ginseng is provided with the description of biological activity of a North American ginseng extract (NAGE), which includes illustrating mechanisms for antioxidant activity without prooxidant properties.