Proliferative vitreoretinopathy (PVR) is a complication of retinal detachment (RD) that is characterized by the development of retinal stiffness and contractile membranes on the surface or underside of the retina. It can occur in primary RD and make repair more challenging, or it can occur following initial successful RD repair and lead to re-detachment. Though our understanding of the pathophysiology underlying PVR membrane formation has grown based on cellular and animal models, there remains no currently approved medical therapy for treatment or prevention of PVR. Though some pharmacologic agents remain under active investigation, many have failed to show consistent benefit in human trials despite promising results from preclinical models. Further research is essential not only to enhance our understanding of PVR pathophysiology but also to identify novel therapeutic strategies for treating PVR in human patients.