At present, surgical separation of the vitreous from the retina (posterior vitreous detachment, PVD) is achieved by mechanical means only. However, with this technique, complete removal of the cortical vitreous from the internal limiting membrane of the retina is not feasible. As incomplete PVD and an attached vitreous cortex are associated with the progression of common retinal diseases including diabetic retinopathy and maculopathy, central retinal vein occlusion and proliferative vitreoretinopathy, induction of complete PVD is a major issue both in vitreoretinal surgery and in medical retina. This chapter focuses on current concepts of pharmacologic vitreolysis. Agents capable of altering the molecular organization of the vitreous are introduced and discussed in terms of PVD induction and liquefaction of the vitreous gel.