The present paper reviews the evidence for anxiolytic activity of 5-HT(3) receptor antagonists in animal models of anxiety and in clinical trials in humans. Compared to the established anxiolytics (benzodiazepine receptor agonists and, to a lesser extent, 5-HT(1A) receptor agonists) 5-HT(3) receptor antagonists display a different anxiolytic profile. They are anxiolytic in a limited number of animal anxiety models. If active, they often are very potent and display bell-shaped dose response curves, whereas the ratio between therapeutic activity and side effects appears remarkably large. 5-HT(3) receptor antagonists remain active after chronic dosing and no indications for tolerance, dependence or rebound effects were found, which seems to make these drugs an attractive alternative to the benzodiazepines. However, the large body of animal data indicating a complete lack of psychotropic activity of 5-HT(3) receptor antagonists weakens the prediction of anxiolytic activity in these drugs. Human data are also controversial; some investigators have reported positive effects in anxiety disorders (panic disorder, GAD), others did not. It can be concluded that 5-HT(3) receptor antagonists do not represent a breakthrough in the treatment of various anxiety disorders, as initially suggested.