PURPOSE OF REVIEW: In contrast to current clinically used tamponades including oils and gases, hydrogels offer a vitreous replacement that has the potential to present a niche for vitreous cells and elevate vitreous substitutes to the level of tissue engineering. This article, therefore, highlights and discusses recent hydrogel-based vitreous replacement strategies as well as the latest progress on vitreous cells, towards the development of a cellularized vitreous substitute. RECENT FINDINGS: A variety of different crosslinked hydrogel systems have been recently investigated as preformed and in situ forming vitreous substitutes, based on biopolymers and/or synthetic polymers. In addition, a comprehensive understanding of the precise function and immunological significance of hyalocytes as vitreous macrophages has recently emerged using advanced imaging techniques and high-throughput transcriptional and protein analyses. SUMMARY: Tissue engineering offers transformative potential for vitreous replacement by combining advanced hydrogel systems with hyalocytes as vitreous cells to further replicate the versatile characteristics and functions of the native vitreous.