Proliferative vitreoretinopathy (PVR) is a blinding disease characterized by the formation of epiretinal membranes through the wound repair process. Though the mechanisms of PVR development are still not fully understood, retinal pigment epithelial (RPE) cells are indicated to play the primary role in the pathogenesis of PVR. In the setting of PVR, RPE cells undergo a process named epithelial-mesenchymal transition (EMT), by which differentiated epithelial cells go through a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts. Recent studies indicated that EMT in RPE cells is a main contributor of PVR and involves various growth factors/cytokines, transcriptional factors, and microRNAs. Targeting these factors/microRNAs suppresses the progression of EMT and thus may provide novel ideas for the treatment of PVR. This review highlights the current understandings of EMT in the pathogenesis of PVR and the underlying mechanisms of EMT in RPE cells.