The genus Polygonum encompasses approximately 300 species widely distributed around the world, among which 120 Polygonum species grow in China. Among the rich species, 81 of them are widely used in traditional Chinese and folk medicines. In recent years, several studies have found that the genus Polygonum posseses a variety of biological activities including antioxidation, antimicrobial, anti-tumor, anti-obesity, etc. However, there are still not enough systemic data on the chemical constituents and their pharmacological effects; hence, it would be useful to review current literature for available pharmacological activites of the genus and as well as its active ingredients. Both in-vitro and in-vivo studies have provided strong evidence for the therapeutic potential of the genus Polygonum. This review collates and examines information on the pharmacological effects of the genus Polygonum as well as its chemical constituents.