Nuclear domains 10 (ND10), alternatively termed PML nuclear bodies (PML-NBs) or PML oncogenic domains (PODs), have been discovered approximately 15 years ago as a nuclear substructure that is targeted by a variety of viruses belonging to different viral families. This review will summarize the most important structural and functional characteristics of ND10 and its major protein constituents followed by a discussion of the current view regarding the role of this subnuclear structure for various DNA and RNA viruses with an emphasis on herpesviruses. It is concluded that accumulating evidence argues for an involvement of ND10 in host antiviral defenses either via mediating an intrinsic immune response against specific viruses or via acting as a component of the cellular interferon pathway.