Ocular infections must be treated with active antibiotics which could be administered by different routes: topical, systemic or intravitreal. In the case of endophthalmitis, the most important factor to avoid permanent damage of retina is an early antibiotic onset. Topical application of these drugs would be ineffective in the treatment of endophthalmitis, because of their poor penetration into the ocular globe. Systemic and intravitreal route of administration are the preferred in this setting, although for hydrophilic antibiotics, such as aminoglycosides, beta-lactams and glycopeptides, diffusion from plasma to vitreous cavity is not high enough to assure clinical efficacy. Intravitreal injection should be the favourite route of administration in this case. Ocular penetration of linezolid and fluorquinolones after systemic administration is excellent; hence intravitreal injections for these agents are not needed to achieve therapeutic concentrations at the vitreous cavity.