Experimental animal models have provided much information that can be applied to antimicrobial therapy of infections of the central nervous system and eye. The efficacy of an antimicrobial agent in the therapy of meningitis depends upon its ability to penetrate the blood-brain barrier, be active in purulent cerebrospinal fluid, and demonstrate rapid bacterial activity against the offending pathogen. In ocular infections, topically administered drugs must overcome various barriers to penetrate into the eye, or these barriers must be bypassed (i.e., by periocular or intravitreal injection) for optimal therapy. This article reviews the basic therapeutic principles for the treatment of infections of the central nervous system and eye, and gives recommendations for the treatment of specific infections.