Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs. Without treatment, inflammation leads to cartilage damage, bone erosions, joint destruction, and impaired movement. Because of the limited success of disease-modifying anti-rheumatic drugs, the exploration of new anti-rheumatic drugs with high efficacy and less toxicity is eagerly needed. Genistein, the major active compound from soybean, has received much attention due to its potential beneficial effects on some of the degenerative diseases. It has been found that genistein has anti-inflammatory, antiangiogenesis, antiproliferative, antioxidant, immunomodulatory, pain relief, and joint protection properties. Hence, significant advances have been made, both by in vitro and in vivo studies showing that genistein is a promising agent for RA treatment.