There are a number of barriers to the ocular transport of poorly lipid-soluble antibiotics such as beta-lactams and aminoglycosides. Knowledge of these barriers can help the physician in the choice of agent and the route of administration for specific ocular infections. Because of the corneal epithelial barrier, topically applied drugs should be administered frequently; "fortified" drops afford higher corneal concentrations than commercially available drops. Periocular injections may occasionally be of benefit in the treatment of refractory corneal ulcers. The mainstay of treatment of bacterial endophthalmitis should be intravitreal injection of antimicrobial agents; ancillary treatments include the periocular and systemic administration of antimicrobial agents, the systemic administration of probenecid, the administration of corticosteroids, and the use of vitrectomy.