We have reviewed the neurobiology of stress ulcers from animal models to potential pharmacotherapeutic mechanisms. The evidence strongly supports the hypothesis that certain stress-related gastric lesions are 'brain-driven' events which may be more effectively managed through central manipulations than by altering local, gastric factors. Recent advances in the use of anxiolytic and antidepressant drugs in the management of stress-related gastric mucosal injury further supports the contention that a brain-gut axis, which may have nervous, peptidergic and classic monoaminergic components, modulates the intricate and complicated pattern of communication between the brain and the stomach. Delineation of the precise pathways which make up this communication as well as their manipulation by various pharmacological agents will be the focus of future research endeavour.