The incidence of preterm birth has remained unchanged for the last few decades. This is due, in part, to the complex etiology of preterm labor, and the limited ability of tocolytic agents to prolong pregnancy as a result of limited efficacy and poor safety profiles. The recent introduction of the oxytocin antagonist, atosiban, represents a new generation of uterine-specific tocolytics, which are associated with more favorable safety profiles. This paper discusses the rationale behind the development of the oxytocin antagonists and provides a review of the phase II and III trials that have investigated atosiban. Also included is a retrospective analysis of 83 women assessed in the Vienna Medical School, providing an insight into the benefits associated with atosiban in the everyday clinical setting. The introduction of a safer tocolytic agent offers the potential to change the current approach to the management of preterm labor. This includes a prolonged period of treatment at earlier or later gestational ages and possibly an extended use to women with contraindications who would normally have been excluded from treatment, e.g. preterm premature rupture of the membranes.