Hormone replacement therapy is still a popular and most effective treatment for vasomotor symptoms and bone loss prevention in the postmenopause but it is not without risks. This has driven many climacteric women to seek for alternatives, chiefly natural products. Phytoestrogens containing soy or red clover preparations, however, when taken at the recommended daily doses, proved to be ineffective to ameliorate climacteric complaints and to prevent osteoporosis. Cimicifuga racemosa (CR) preparations, on the other hand, have been shown to ease climacteric distress. There is a widespread, but false, belief that the efficacy of CR preparations is linked to the presence of phytoestrogens in the plant. This review aims at summarizing the available in vitro and in vivo evidence showing that compounds in CR extracts do not bind to oestrogen receptors and thus do not exert any estrogenic effects in the uterus and mammary gland, as shown in vivo in experiments on ovariectomized rats and clinically in postmenopausal women. Studies in ovariectomized rats and in women suffering from climacteric complaints have indicated that substances with neurotransmitter-like activities affect beneficially postmenopausal symptoms such as hot flushes. Some of these compounds, such as actein-like triterpenes with GABA-ergic activity and a serotonin analogue, are present and have been identified in the CR extracts. We conclude that these activities explain most likely the beneficial effects of CR extracts on climacteric complaints.