This chapter is focused on the relatively recent investigations demonstrating a pharmacological and pathophysiological role for bFGF and PDGF in ulcerative and inflammatory lesions in the upper and lower GI tract. Our initial animal model experiment revealed a potent healing of chronic cysteamine-induced duodenal ulcer in rats treated by intragastric administration of bFGF-w, the acid-resistant bFGF-CS23 or PDGF-BB without decreasing gastric acid secretion or concentration. Subsequently we and others have demonstrated that these peptides accelerate the healing of chronic gastric ulcers, chronic erosive gastritis and ulcerative colitis. Contrary to the potent ulcer healing properties of bFGF and PDGF, these growth factors exert no or modest acute gastroprotection. Nevertheless, new biochemical, molecular biological and immunohistochemical studies indicate that both bFGF and PDGF play a pathophysiological role in the natural history of ulcer healing.