In patients who present with chronic unexplained upper abdominal pain or discomfort (functional dyspepsia), therapy should ideally be targeted on correcting the individual's disturbed pathophysiology. Here, putative mechanisms implicated in functional dyspepsia and potential approaches to therapy are critically reviewed in order to determine if targeting treatment is of value. Pharmacological therapies reviewed include those that aim to correct disordered gastric emptying (e.g. cisapride, dopaminergic receptor antagonists, macrolides), reduce visceral hypersensitivity (e.g. somatostatin analogues, cholecystokinin antagonists, opioid agonists, serotonin type 3 receptor antagonists), reduce gastric acid secretion (e.g. H2-blockers, acid pump inhibitors), cure Helicobacter pylori infection, enhance muscosal defence (e.g. sucralfate, bismuth) or modify central nervous system processes. It is concluded that the imperfectly understood pathophysiology of functional dyspepsia contributes to the paucity of established efficacious therapies.