Posterior vitreous detachment (PVD) is the consequence of changes in the macromolecular structure of gel vitreous that result in liquefaction, concurrent with alterations in the extracellular matrix at the vitro-retinal interface that allow the posterior vitreous cortex to detach from the internal limiting lamina of the retina. Gel liquefaction that exceeds the degree of vitro-retinal dehiscence results in anomalous PVD (APVD). APVD varies in its clinical manifestations depending upon where in the fundus vitreo-retinal adhesion is strongest. At the periphery, APVD results in retinal tears and detachments. In the macula, APVD causes vitreo-macular traction syndrome, results in vitreoeschisis with macular pucker or macular holes, or contributes to some cases of diabetic macular edema. At the optic disc and retina, APVD causes vitreo-papillary traction and promotes retinal and optic disc neovascularization. Unifying the spectrum of vitreo-retinal diseases into the conceptual frame-work of APVD underscores that to more effectively treat, and ultimately prevent, these disorders it is necessary to replicate the two components of an innocuous PVD, i.e., gel liquefaction and vitreo-retinal dehiscence. Pharmacologic vitreolysis is designed to mitigate against APVD by chemically breaking down vitreous macromolecules and weakening vitro-retinal adhesion to safely detach the posterior vitreous cortex. This would not only facilitate surgery, but if performed early in the natural history of disease, it should prevent progressive disease.