Vitreoretinal surgeries for ocular diseases such as complicated retinal detachment, diabetic retinopathy, macular holes and ocular trauma has led to the development of various tamponades over the years in search for an ideal vitreous substitute. Current clinically used tamponade agents such as air, perfluorocarbons, silicone oil and expansile gases serve only as a short-term solution and harbors various disadvantages. However, an ideal long-term substitute is yet to be discovered and recent research emphasizes on the potential of polymeric hydrogels as an ideal vitreous substitute. This review highlights the recent progress in the field of vitreous substitution. Suitability and adverse effects of various tamponade agents in present day clinical use and biomaterials in the experimental phase have been outlined and discussed. In addition, we introduced the anatomy and functions of the native vitreous body and the pathological conditions which require vitreous replacement.