Human vitreous is a natural intraocular polymeric hydrogel with distinct biochemical and physiological functions. Surgical removal of the vitreous, or vitrectomy, is now commonly performed for the treatment of many vitreoretinal diseases. This has led to the need for developing substances that can be used to replace vitreous. Although early attempts for vitreous transplantation have yielded little success [1], a range of other vitreous substitutes has been developed. An ideal substitute should have all the good qualities of the human vitreous, including transparency, elasticity, buffer capacity, and biocompatibility with surrounding ocular tissues. However, none of the currently available vitreous substitutes possesses all these qualities. In modern vitreoretinal surgery, both short-acting (e.g., air, balanced salt solutions, expansile gases) and long-acting vitreous substitutes (e.g., silicone oil) are used. All these substitutes have significant shortcomings, mostly related to the lack of local biocompatibility and inadequate physiological role. In this chapter, we discuss the biophysical, biochemical, and physiological properties of the available vitreous substitutes, as well as their clinical use, advantages, and limitations. A separate chapter addresses the future potential of an artificial vitreous [see chapter I.F. Vitreous biochemistry and artificial vitreous].