Infections of the central nervous system (CNS) can be rapidly progressive, RESULTing in death or permanent neurological damage in a short period of time, because of focal immunocompromised milieu with few complements and immunoglobulins in the cerebrospinal fluid. In order to provide effective antimicrobial therapy in a timely manner, all clinicians need to have a basic understanding of the antimicrobial agents and epidemiological data of the disease. It takes time to reveal the causative organisms of the infection. One should start antimicrobial treatment empirically as soon as possible after collecting the specimens from the patient. Many factors influence the choice of antimicrobial agents in the treatment of the infection which include microorganisms, environmental factors, and host factors such as age, sex, site of infection, and the underlying disease of the patient. Especially, in CNS infections, the efficacy of an antimicrobial agent depends upon its ability to penetrate the blood-brain barrier. The antimicrobial agent should also be active in purulent cerebrospinal fluid and demonstrate rapid bactericidal activity against the offending pathogen. The recent emergence of resistant pathogens, (also seen in Korea), has posed a challenge to the antimicrobial therapy. Therefore, the guidelines of antimicrobial therapy should be suitable for these considerations. This article reviews the basic therapeutic principles for the treatment of infections of the CNS and gives recommendations for the treatment of specific infections.