Ginsenoside Rh2 (G-Rh2) is a natural bioactive product derived from Panax ginseng Meyer (P. ginseng). G-Rh2 exhibits anticancer activity in various human cancer cell lines both in vitro and in vivo by modulating several signaling pathways, such as those of PDZ-binding kinase/T-LAK cell-originated protein kinase, phosphatidylinositol 3-kinase, protein kinase B, mammalian target of rapamycin, epidermal growth factor receptor, p53, and reactive oxygen species. Moreover, G-Rh2 could effectively reverse drug resistance and enhance therapeutic effects in cancer therapy. This review summarizes the chemical properties, in vitro and in vivo anticancer activity, and underlying molecular mechanisms of G-Rh2 to facilitate cancer chemoprevention studies.