In the absence of posterior vitreous detachment, vitreous cortex is adhered to the internal limiting lamina of the inner retina. This junction between the vitreous and the retina is thought to participate in the pathophysiology of diverse retinal diseases, including proliferative diabetic retinopathy and diabetic macular edema. Vitrectomy has been associated with decrease of macular edema and improvement of visual acuity in eyes of diabetic patients. Thus, many pharmacologic agents have been studied with the aim of inducing a posterior vitreous detachment in order to facilitate the surgical procedure and reduce complications of vitrectomy. More recently, different agents such as plasmin and microplasmin have shown to be able to induce a posterior vitreous detachment given as a single intravitreal injection. The aim of this article is to give a scope about the pharmacologic vitreolysis and posterior vitreous detachment studies and describe some ongoing clinical trials that will determine the efficacy and safety of these novel therapies for diabetic retinopathy.