Abstract: Xa21 was the first disease resistance gene cloned from rice, which encodes a receptor-like kinase and confers broad spectrum resistance against Xanthomonas oryzae pv. oryzae (Xoo). In this paper, the discovery, mapping and cloning of Xa21 were reviewed briefly, and the molecular mechanism of resistance and its breeding application, including biochemical properties of the kinase domain of XA21, AvrXa21 identification, the disease resistance pathway mediated by Xa21, and the mechanism of disease resistance were summarized. The future perspective on Xa21-related research is also discussed.