Rapid advances have been achieved in the therapy of herpes virus infections of children over the past 25 years. Following the demonstration that vidarabine was an efficacious treatment for neonatal herpes simplex virus (HSV) infections, herpes simplex encephalitis, and varicella zoster virus (VZV) infections of children, significant advances were achieved with the development of second generation anti-viral drugs. The second generation anti-viral drug, namely acyclovir, and, subsequently, valacyclovir and famciclovir, now provide both efficacious as well as safe anti-viral therapy for a variety of herpes virus infections. More recently, the demonstration that ganciclovir proved efficacious for the treatment of congenital cytomegalovirus (CMV) infections provides impetus for improving therapeutics for the most common congenital infection of humans. The therapeutic advances achieved in the management of neonatal HSV infection, herpes simplex encephalitis, VZV infections of the normal and immunocompromised host, and congenital CMV infection will be summarized in this review. © 2008 Springer Science+Business Media, LLC.