The eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment models of ocular drug delivery have been developed for describing the absorption, distribution, and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems, and routes of administration is discussed including factors affecting intraocular bioavailability. Factors such as precorneal fluid drainage, drug binding to tear proteins, systemic drug absorption, corneal factors, melanin binding, and drug metabolism render ocular delivery challenging and are elaborated in this manuscript. Several compartment models are discussed; these are developed in ocular drug delivery to study the pharmacokinetics parameters. There are several transporters present in both anterior and posterior segments of the eye which play a significant role in ocular pharmacokinetics and are summarized briefly. Moreover, several ocular pharmacokinetics animal models and relevant studies are reviewed and discussed in addition to the pharmacokinetics of various ocular formulations.