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Ganoderma lucidum (G. lucidum) is a medicinal fungus showing a variety of biological functional activities, and has being used for millennia as a folk remedy for promotion of health and longevity. One of the most attractive characters of G. lucidum is its diverse immune-modulatory activity. These phenomena suggest G. lucidum may contain different active components that can be prepared from different extraction methods with distinguished immune-modulatory activity. Using NK-92, a natural killer (NK) cell line, as the study model, we set out to evaluate the effect of three G. lucidum extracts on NK cell activity. NK-92 cells pretreated with aqueous G.lucidum extracts demonstrate enhanced cytotoxicity against a panel of tumor targets in vitro in a dose dependent manner. Results from these studies indicate the presence of bioactive components in the aqueous extract that have stimulatory immune-modulation activities. Further studies will aim at purification and characterization of these active components from both G.lucidum aqueous extracts.