PURPOSE: To reexamine the role of the vitreous gel in ocular health and disease based on recent information in the ophthalmic literature. DESIGN: Perspective. METHODS: Review, analysis, and discussion of the implications of selected pertinent literature. RESULTS: A new understanding of the vitreous gel is emerging, placing it central to many disease processes affecting the eye, including diabetic retinopathy, retinal vein occlusion, age-related macular degeneration, nuclear sclerotic cataract, and primary open-angle glaucoma. The vitreous gel recently has been found to have the important function of oxygen regulation and distribution within the eye. As the gel undergoes age-related liquefaction or surgical removal this function is impaired. The resultant elevated intraocular oxygen tension likely proves beneficial for vascular endothelial growth factor-mediated retinal diseases. However, it may lead to oxidative stress within the eye and may contribute to disease states such as nuclear cataract and primary open-angle glaucoma. CONCLUSIONS: An intact gel vitreous is central to a healthy human eye. We now understand that age-related liquefaction of the vitreous gel accompanies several age-related ocular diseases. The field of ophthalmology would benefit from future research to understand age-related vitreous liquefaction and to identify its cause.