Topical dosing of ophthalmic drugs to the eye is a widely accepted route of administration because of convenience, ease of use, and non-invasiveness. However, it has been well recognized that topical ocular delivery endures a low bioavailability due to the anatomical and physiological constraints of the eye which limit drug absorption from the pre-corneal surface. Nonionic surfactants as versatile functional agents in topical ocular drug delivery systems are uniquely suited to meet the challenges through their potential ability to increase bioavailability by increasing drug solubility, prolonging pre-corneal retention, and enhancing permeability. This review attempts to place in perspective the importance of polyoxyethylated nonionic surfactants in the design and development of topical ocular drug delivery systems by assessing their compatibility with common ophthalmic inactive ingredients, their impact on product stability, and their roles in facilitating ocular drugs to reach the target sites.