The uterus undergoes dynamic tissue remodeling throughout each reproductive cycle, which is regulated in part by the matrix metalloproteinases (MMP) system. The MMP system is comprised of the proteolytic factors, the MMPs, and their tissue inhibitors (TIMPs), which act in concert to modulate extracellular matrix turnover and cell behaviors and thus play a key role in many physiologic and pathologic conditions throughout the body. MMPs and TIMPs are expressed spatiotemporally in the uterus of various menstruating and non-menstruating species. The balanced function of the MMP system is critical to normal uterine tissue remodeling throughout the cycle as well as during pregnancy, parturition and postpartum uterine involution. The uterine MMP system appears to be under the regulation of not only ovarian steroids but also various autocrine/paracrine factors such as growth factors, cytokines and chemokines. The current review focuses on the expression and regulation of the MMP system within the uterus during the menstrual or estrous cycle, and addresses the roles of various MMPs and TIMPs in uterine biology.