Drug delivery for the treatment of posterior segment diseases has become a major challenge in the field of ophthalmology due to its restrictive barrier functionalities. Blood-ocular barriers act as a physical barrier between the local blood vessels, ocular tissues and fluids which restrict the passage of various solutes and fluids. Ocular barriers may be classified as static and dynamic barriers. Static barrier include sclera, Bruch’s membrane-choroid (BC), retinal pigment epithelium (RPE) and conjunctiva while dynamic barriers include drug clearance mechanism through blood and lymphatic vessels. Apart from above mentioned barriers, it is also imperative to understand the role of enzymes and transporters in drug disposition. Overall, it is essential to understand anatomy, physiology and disposition mechanisms of eye and interaction between drug molecules/formulation with various ocular tissues in order to design a successful drug delivery system.