Benzodiazepines have been involved during the years in the prevention and treatment of Post-Operative Nausea and Vomiting (PONV). Midazolam, a short acting benzodiazepine widely used as a premedicant before surgery, for induction of anaesthesia, and for conscious sedation, has been particularly studied, sometimes with conflicting results. This paper will discuss the possible mechanisms of action of midazolam in PONV management and its fields of application (adults and children undergoing surgery, treatment of persistent postoperative emesis), as far as potentialities of other non-traditional anti-emetics, maybe ready to get out the arena of case reports, and the need of further studies on postoperative anti-emetics in their efficacy in treating established PONV.