Conventionally, antimicrobial drugs developed and approved for systemic infections are re-investigated for ocular infections. However, developing a new antimicrobial agent with good intraocular penetration by considering the anatomical and physiological constraints exerted by the barriers of eye is not a popularly perceived strategy. For the last three to four decades much emphasis has been placed on drug delivery systems to enhance the ocular penetration of antimicrobial agents. In order to compare ocular drug delivery strategies for ocular infections, the existing studies and methods were revisited using an extensive literature search. The present analysis also encompasses the scientific outcomes of endophthalmitis studies to interpret the intraocular penetration data of various antimicrobial agents and their requirements before and after the onset of inflammation. This article critically analyses the systemic and topical drug delivery methods adopted for antimicrobial use and their applicability to the newer class of antimicrobial agents, thus giving space for further developments. This review emphasizes the requirement of stage-by-stage insights about ocular infections, the need for an eye-specific antimicrobial agent and the inevitability of an appropriate drug delivery approach to revolutionize future therapy.