Proliferative vitreoretinopathy is a disease process that follows the proliferation of ectopic cell sheets in the vitreous and/or periretinal area, causing periretinal membrane formation and traction, in patients with rhegmatogenous retinal detachments. Currently, vitreous surgery is the standard treatment; however, the results aren't satisfactory given the vision loss that ensues and that redetachment is relatively common. It is becoming clearer that there exists an interplay between various cytokines/growth factors, matrix proteins, and the different cell types that drive the undesirable formation of periretinal membranes. This fundamental understanding is aiding in identifying different adjunct agents that can block the cellular events intrinsic to proliferative vitreoretinopathy. In this review, we describe the current understanding on the pathogenesis and discuss how the fundamental understanding of the biochemical/molecular events is instrumental in developing the novel treatment strategies that are also highlighted.