It is unknown why ulcers in general heal. Some clues are worth considering. What is known is (i) that ulcer healing occurs spontaneously, (ii) that ulcers heal more quickly in the duodenum than in the stomach, (iii) that mucosal blood flow at ulcer edge improves with healing, and (iv) that healing can be speeded up by (a) not smoking, (b) removing acid from the stomach, and (c) using non-antisecretory mucosal protective agents such as sucralfate and colloidal bismuth. The difference in healing rates between duodenal and gastric ulcers may be related to ulcer size, duodenal alkalinity due to the secretion of the Brunner's glands, and other uninvestigated factors such as epidermal growth factor and mucosal blood flow. The difference between smokers and non-smokers may be related to inhibition of prostaglandin synthesis and impairment of mucosal blood flow due to smoking and to higher acid secretion in smokers. The success with antisecretory agents indicates that acid inhibits the healing process. The success of sucralfate and bismuth indicates that cytoprotective mechanisms play a role in ulcer healing. The literature also shows that ulcer healing is less affected by smoking in patients treated with sucralfate than in those treated with antisecretory agents, suggesting that cytoprotective mechanisms play a more important part than acid inhibition in counteracting the adverse effects of smoking on healing. Furthermore, ulcer relapse occurs sooner in patients treated with antisecretory agents than in those treated with sucralfate or bismuth, suggesting that withdrawal of antisecretory agents speeds up relapse and/or that cytoprotective mechanisms are associated with longer-lasting remission. It is concluded that sucralfate healing involves cytoprotective mechanisms and that these cannot be ignored in the planning of any anti-ulcer therapy. Despite the understanding of the various site-protective and cytoprotective mechanisms, as discussed in the previous article, it is not clear why ulcers heal with sucralfate. In fact, there is no clear answer to the fundamental question as to why ulcers in general heal with the known therapeutic agents, including H2-receptor antagonists, antacids, proton pump inhibitors, anticholinergics, site-protective agents, and cytoprotective agents. This review examines this question, using sucralfate as a model.