Portal hypertensive gastropathy (PHG) is recognized as a clinical entity in portal hypertension, but the pathogenesis of PHG is still unclear. Therefore, we reviewed the current state of knowledge concerning the portal hypertensive gastric mucosa and hypothesized the pathogenesis of PHG. Elevated portal pressure can induce changes of local hemodynamics, thus causing congestion in the upper stomach and gastric tissue damage. These changes may then activate cytokines and growth factors, such as tumor necrosis factor alpha, which are substances that activate endothelial constitutive nitric oxide synthase and endothelin 1 in the portal hypertensive gastric mucosa. Overexpressed nitric oxide synthase produces an excess of nitric oxide, which induces hyperdynamic circulation and peroxynitrite overproduction. The overproduction of peroxynitrite, together with endothelin overproduction may cause an increased susceptibility of gastric mucosa to damage. When combined with the characteristics of impaired mucosal defense and healing, these factors may together produce PHG in patients with portal hypertension.