The present review describes the morphological, phytochemical and ethnopharmacological aspects of Humulus lupulus L. (Cannabinaceae) and summarizes the most interesting findings obtained in the preclinical and clinical research related to the plant. The female inflorescences of Humulus lupulus (hops), well-known as bittering agent in brewing industry, have long been used in traditional medicine mainly to treat sleep disturbances. However the sedative activity is still under investigation in order to recognize the active principles responsible for the neuropharmacological effects observed in laboratory animals, and their mechanism of action. Here we report the data from our experiments as well as those obtained from other researchers, focusing on the variability of the results. Other traditional applications of hops as stomachic, antibacterial and antifungal remedy have been supported by in vivo and/or in vitro investigations. In recent years some prenylated chalcones present in hops have received much attention for their biological effects: in particular, xanthohumol has been shown to exert cancer chemopreventive activity in in vitro experiments, while 8-prenylnaringenin has been characterized as one of the most potent phytoestrogens isolated until now. Nevertheless much additional work is needed to open up new biomedical application of these compounds.