Preterm birth and postpartum hemorrhage are the leading causes of neonatal and maternal morbidities worldwide, respectively. Current clinically utilized tocolytics and uterotonics to manage these obstetric conditions are limited due to their off-target effects and/or lack of efficacy. Thus, an ideal tocolytic or uterotonic would be uterine-selective with rapid onset and long-duration efficacy. Here, we discuss strategies for the discovery of new therapeutic targets and compounds that regulate uterine contractility with the aforementioned properties.