First investigations to treat diseases of the posterior segment enzymatically started 40 years ago. Increasing experience with pars plana vitrectomy demonstrated that a complete removal of the vitreous body has beneficial effects on the course of various proliferative vitreoretinal diseases. Therefore enzymes were tested to either liquify the vitreous body (collagenase or hyaluronidase) or to cleave posterior vitreous cortex and retina (dispase, plasmin, tissue plasminogen-activator or chondroitinase). At present only tissue-plasminogen activator (TPA), plasmin and hyaluronidase were used in small clinical studies. Recent developments in the understanding of vasoproliferative vitreoretinal disorders offers new therapeutical approaches like enzymatically destruction of growth factors or extracellular adhesive proteins (fibronectin). From this point of view future therapies may include enzymatic cleaning of the vitreous to prevent proliferative diabetic vitreoretinopathy.To treat acute subretinal hemorrhage a pneumatic displacement through intravitreally injected gas after enzymatically induced subretinal fibrinolysis (TPA) is recommended__í. Recent morphometric analysis clearly demonstrated a subretinal fibrinolytic effect after intravitreal injection of TPA. Obviously TPA crosses the retina through microlesions that develop through elevation of the retina during acute bleeding. For the first time pars plana vitrectomy was superseded by a simple and gentle enzymatic therapy combined with pneumatic displacement by intravitreally injected gas.