Studies report that 40-100% of the general population are infected with cytomegalovirus (CMV), a virus associated with severe neurological conditions, such as CMV encephalitis, and which may have a role in some cases of Guillain-Barre syndrome. CMV infection is a particular concern among individuals with HIV, as almost all are co-infected with it. The introduction of highly active antiretroviral therapy (HAART) has provided a means of reconstituting the immune system of those with HIV/AIDS in such a way as to allow CMV infection to be controlled. In doing so, HAART has done much to reduce the mortality rate associated with CMV disease in such patients. Despite this, response to treatment in these patients remains suboptimal and many do not have access to such therapy, so, efforts to improve the treatment of CMV have been a priority. The International Herpes Management Forum (IHMF) has developed management guidelines to promote the improved diagnosis and treatment of CMV disease of the central nervous system (CNS). It is recommended that polymerase chain reaction (PCR) for viral DNA should be performed on CSF as a means of diagnosing CMV infection of the CNS. As CMV disease is always preceded by viraemia, treatment should be directed toward the prevention of CMV disease. However, if CMV disease develops, ganciclovir is recommended as therapy and continued in a maintenance fashion, which can be discontinued should CD4 count remain above 100 cells/mm3 for 6 months. In many circumstances, valganciclovir may be preferred, depending on the level of function in the patient, their ability to take oral therapy and the severity of disease. Use of foscarnet should be limited to ganciclovir-resistant cases due to the high level of toxicity associated with the drug and its intravenous mode of administration.