Herpesvirus infections are a known cause of significant morbidity in the immunocompromised host, including those with human immunodeficiency virus (HIV) or AIDS. While acyclovir has been available for some time and provides significant benefit for individuals with herpes simplex and variccella-zoster virus infectors, the need for improved therapeutics which address the ever evolving problems associated with antiviral resistance and improved therapies for cytomegalovirus (CMV) retinitis requires special note. Current problems in the management of herpesvirus infections focus, in general, on five specific areas. First, it has been recognized that herpes simplex viruses can acquire resistance to acyclovir, particularly with prolonged use. Progressive clinical disease can be encountered in individuals who develop thymidine kinase-altered herpes simplex virus isolates. As a consequence, new and improved therapeutics for herpes simplex virus infections, particularly with novel mechanisms of action, warrant introduction. Secondly, management of CMV retinitis has focused, historically, on the utilization of drugs such as gangciclovir and foscarnet. The recent availability of cidofovir, which can be administered intermittently, may provide a treatment regimen of greater acceptability to those individuals who suffer from CMV retinitis. Fortunately, newer antiviral drugs are under development which will allow for oral administration. Thirdly, new drugs are becoming available for the treatment of herpes zoster in HIV-infected individuals. Sorivudine has been evaluated for the treatment of herpes zoster in individuals with HIV infection. The availability of this drug for targeted patient populations will provide a therapeutic regimen allowing for once-daily dosing. Fourthly, the use of anti-herpetic agents, particularly acyclovir, has been employed with antiretroviral therapy in order to potentially decrease associated cofactors (e.g. CMV, human herpesvirus (HHV)-6 etc.) Finally, the recent discovery of HHV-8 and its association with Kaposi's sarcoma provides unique avenues for further investigation. Improvements in all of these areas will result in improved quality of life for individuals with HIV infections and AIDS.