Ophthalmic drugs typically achieve < 10% ocular bioavailability. A drug applied to the surface of the eye may cross ocular-blood barriers where it may encounter metabolising enzymes and cellular transporters before it distributes to the site of action. Characterisation of ocular enzyme systems and cellular transporters and their respective substrate selectivity have provided new insight into the roles these proteins may play in ocular drug delivery and distribution. Altered metabolism and transport have been proposed to contribute to a number of ocular disease processes including inflammation, glaucoma, cataract, dry eye and neurodegeneration. As ocular enzyme and transport systems are better characterised, their properties become an integral consideration in drug design and development.