Antiviral agents against human herpesviruses (HHVs) include acyclovir, cidofovir, and foscarnet. Human herpesviruses are DNA viruses in the Herpesviridae family. Herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and HHV-8 belong to the Herpesviridae family. Antivirals against the group generally act via inhibition of DNA polymerase. Acyclovir (the prototypical nucleoside analog) requires viral kinase for phosphorylation to become a triphosphate, which is incorporated in viral DNA. Cidofovir requires phosphorylation by host cellular kinase, which allows cidofovir to have activity against mutated viruses and become deficient in viral kinase. Foscarnet (a pyrophosphate analog) does not require phosphorylation. Nephrotoxicity is a shared adverse effect in the agents. Acyclovir can also cause obstructive crystalline nephropathy and foscarnet carries a risk of electrolyte abnormalities and seizures. The nephrotoxic effect of cidofovir can be reduced with IV saline and probenecid.