PML nuclear bodies (PNBs) are proteinaceous structures which predominantly reside inside the nuclei of mammalian cells. Their antiviral effects on a wide range of DNA and RNA viruses are shown. Viruses have evolved a diverse range of mechanisms to overcome the antiviral effect of PNBs. In particular, herpesviruses enter into an association with PNBs to control such antiviral effects. An outcome of this association is switching between the two life cycles of the virus. In this manuscript, we have reviewed our current knowledge on the biology of PNBs and the interplay between them and herpesviruses with an emphasis on the factors that affect the life cycle of the virus.