Selective serotonin 5-HT3receptor antagonists have proven safe and effective for the management of postoperative nausea and vomiting. Dolasetron, granisetron, ondansetron and tropisetron selectively and competitively bind to 5-HT3receptors, blocking serotonin binding at vagal afferents in the gut and in the regions of the CNS involved in emesis, including the chemoreceptor trigger zone and the nucleus tractus solitarii. Despite their shared mechanism of action, 5-HT3receptor antagonists have different chemical structures and exhibit differences in receptor binding affinity, dose response and duration of effect. Furthermore, although dolasetron, granisetron, ondansetron and tropisetron are all extensively metabolised by the cytochrome P450 (CYP) system, different components of this system predominate in the metabolism of each of these agents. Hence, although these agents are considered equally effective in the overall population, their pharmacokinetic and pharmacodynamic differences may explain the variability in individual responses to these drugs. This review discusses the pharmacological profiles of dolasetron, granisetron, ondansetron and tropisetron, and the clinical implications of differences in their profiles.