Magnetic resonance imaging has revealed that the endometrio-myometrial interface constitutes a distinct, hormone-dependent uterine compartment termed the junctional zone. In the non-pregnant uterus, highly specialized contraction waves originate exclusively from the junctional zone and participate in the regulation of diverse reproductive events, such as sperm transport, embryo implantation, and menstrual shedding. Conversely, growing evidence suggests that disruption of the normal endometrio-myometrial interface plays an integral role in diverse reproductive disorders. This chapter reviews our current understanding of the mechanisms that govern the cyclic changes in the uterine junctional zone and summarizes the evidence implicating the endometrio-myometrial interface in normal uterine physiology and pathological processes.