Despite significant advances in the understanding of uterine physiology, preterm labor is still a predicament with a high incidence. The mechanism that triggers uterine contraction is currently unclear. ATP-sensitive potassium (KATP) channel stimulation has an inhibitory effect on uterine contractile pursuit through hyperpolarization of myometrial cells where KATP channels openers (KCOs) act as a tocolytic. In this review, studies that report the effects of KCOs on the contractile activity of the myometrium have been collected and evaluated. All electronic databases were searched up to 1(st)December 2012 with the most relevant keywords. Studies related to the effect of KCOs on the human or animal myometrium both in vivo and in vitro were included. Of initial search, 45 records were reviewed and finally, 23 were included. All of these studies found that KCOs have an inhibitory effect on the myometrium contractions, but different sample size and inconsistencies in reporting the effects make the absolute judgment about efficacy of these compounds too difficult. Of course, we can state that the inhibitory effects of KCOs were greater in myometrium of non-labor group. Conclusion is that although some positive effects are expected, yet further placebo-controlled studies are needed to reach a consensus.