Stress activates hypothalamic-pituitary-adrenal (HPA) axis and subsequently increases the systemic levels of glucocorticoids. It also inhibits the release of gonadotropin-releasing hormone (GnRH) from hypothalamus. Korean ginseng (Panax ginseng CA Meyer) has been proven as an anti-stress agent. However, most of the anti-stress effects of ginseng on stresses such as immobilization, electronic foot shock, and cold swim, which subsequently cause oxidative damage in brain, were obtained by using ginseng extract or ginseng total saponin. Moreover, anti-stress and anti-oxidative effects of ginseng were demonstrated by determination of enzyme or hormone levels but not mRNA as well as transcriptome. Further studies on transcriptome, proteomics, and systems biology as well as signal transduction would be required to elucidate molecular action mechanisms of ginseng on stresses.