Although numerous advances have been made in technology and techniques of pars plana vitrectomy and tamponades, there are still unsolved issues, such as proliferative vitreoretinopathy (PVR), multiple retinal breaks and persistent hypotonia. All available internal tamponades (e.g, gases, oils and fluorocarbons) are hydrophobic, so they approximate the neurosensory retina to the retinal pigment epithelium due to buoyant force and surface tension. Even though these tamponade materials exhibit various beneficial attributes in the clinical application, the hydrophobic nature has clear disadvantages and compartmentalization and significant incidence of PVR development still occur.An ideal vitreous body substitute should mimic the native human vitreous body, in both form and function. Vitreous body substitutes, such as hydrogels fulfill the biophysical needs in a similar manner to the natural vitreous body by providing an internal tamponade effect through swelling pressure and viscosity. New approaches range from cross-linked semisynthetic to synthetic polymers. These hydrogels have a good biocompatibility, optical clarity, a refractive index and rheological properties that are similar to the natural human vitreous body and are able to act as anti-adhesive and anti-migrative agents and can therefore reduce PVR. Furthermore, hydrogels could also serve as controlled-release drug-delivery systems for anti-proliferative, neuroprotective or nutritive drugs.