Pelvic organ prolapse (POP) is a prevalent and disabling condition. The pathophysiology of prolapse is multifactorial, and no single mechanism adequately explains all aspects of its development. The pathophysiology of POP is complex and incompletely understood. Smooth muscle (SM), an integral part of the vaginal wall and endopelvic structures that support the pelvic viscera, has also been implicated in the pathophysiology of POP. In this article, we review the role of smooth muscle cells (SMC) in the pathophysiology of POP, also addressing the anatomy of SM in pelvic floor, morphometric analysis, biomechanical properties, and potential mechanisms.