The treatment of many ocular disorders is hampered because of poor penetration of systemically administered drugs into the eye. The tight junctional complexes (zonulae occludens) of the retinal pigment epithelium and retinal capillaries are the site of the blood-ocular barrier. This barrier inhibits penetration of substances, including antibiotics, into the vitreous. Over the last 18 years we have evaluated the nontoxic doses of various drugs. These include antibiotics and antifungals for treatment of bacterial and fungal endophthalmitis, antivirals for treatment of viral retinitis (specifically, when medication with these drugs poses the threat of toxicity to other organs). Intravitreal antineoplastic drugs have been studied to prevent cell proliferation in the vitreous cavity after retinal attachment surgery, which can lead to proliferative vitreoretinopathy (PVR). Furthermore, we evaluated the anti-inflammatory action of dexamethasone and cyclosporine A to reduce intraocular inflammation after intraocular surgery or in uveitis. Because these studies had been performed in the presence of the vitreous, which can slow down the diffusion of the drugs toward the retina, it was necessary to reevaluate the concentration of drugs which could be administered intravitreally in the vitrectomized eye. The nontoxic dose of numerous drugs when added to vitrectomy infusion fluid has also been evaluated. Furthermore, the role of vitrectomy in the treatment of bacterial fungal endophthalmitis has been studied and the role of vitrectomy in this ocular disorder is defined.