The vitreous humor represents a significant barrier to the penetration of nanoparticulate-based ocular drug delivery systems. The gel structure and biochemical components of the vitreous will impact the rate of nanoparticle movement through the tissue to reach the retinal tissue. Also the structure of the vitreous, flow systems operating within it, age-related structural changes, and the presence of inflammation will also have a potential effect on movement. To effectively target the posterior retina, the physical properties of the nanoparticle formulation are a key element in the design of a system that will penetrate through the vitreous barrier.