The main aim of pharmacotherapeutics is the attainment of effective drug concentration at the intended site of action for a sufficient period of time to elicit a response. Poor bioavailability of drugs from ocular dosage form is mainly due to the tear production, non-productive absorption, transient residence time, and impermeability of corneal epithelium. Though the topical and localized application are still an acceptable and preferred way to achieve therapeutic level of drugs used to treat ocular disorders but the primitive ophthalmic solution, suspension, and ointment dosage form are no longer sufficient to combat various ocular diseases. This article reviews the constraints with conventional ocular therapy and explores various novel approaches, in general, to improve ocular bioavailability of the drugs, advantages of vesicular approach over these and the future challenges to render the vesicular system more effective.