Drug delivery to the eye is challenging due to immediate drainage of eyedrops from the eye, low volume of the cul-de-sac (10–20 µl), the sensitivity of the corneal layer, physicochemical properties of a drug, biological barriers, need for repeated instillation, which finds difficulties for patients. Furthermore, it is difficult to carry drugs across the blood–retinal barrier, and across the cornea when administered systemically and topically, respectively, due to the limited absorption rate at a targeted site. Owing to the static and dynamic constraints associated with the eyes, the permeation of therapeutics to the back of the eye is limited. The use of drug delivery systems that can remain in contact with the ocular surface for a prolonged duration can greatly reduce the frequency of dosing, whereas drug delivery systems that cross ocular barriers may provide greater efficacy of administered drugs to inaccessible ocular tissues. In this review, we explored barrier properties of the ocular tissues, as well as the various drug transport mechanisms in the eye to design an effective strategy. This followed a discussion on the recent strategies to enhance the ocular distribution of therapeutics and have a future for translational nanomedicine. Graphical abstract