In spite of a century of recorded attempts to replace the vitreous body of the eye with a foreign material, there is no permanent substitute currently available, and the success of some materials as temporary substitutes is still very limited. Among the large number of materials proposed or tested as vitreous substitutes, synthetic polymers have been episodically considered during the past four decades. This article will review these attempts, their outcomes, and recent progress in this field. There were only seven synthetic polymers and a few semisynthetic polymers (modified biopolymers) so far proposed or tested as vitreous substitutes. It appears that probably a synthetic hydrogel with very high water content would eventually be the material of choice for a permanent vitreous substitute, but the ideal material has not yet been found.