Monodnaviria is a realm of viruses that includes all single-stranded DNA (ssDNA) viruses encoding an endonuclease from the HUH superfamily, which initiates rolling circle replication of the circular viral genome. The realm also includes viruses derived from such ssDNA viruses, including certain linear ssDNA viruses and circular double-stranded DNA (dsDNA) viruses, although these atypical members replicate through mechanisms other than rolling circle replication. Established in 2019, Monodnaviria is divided into four kingdoms: Loebvirae, Sangervirae, Trapavirae, and Shotokuvirae. The first three kingdoms are composed of viruses that infect prokaryotes, while Shotokuvirae contains viruses that infect eukaryotes, including atypical members of the realm. Viruses in Monodnaviria are believed to have evolved independently multiple times from circular bacterial and archaeal plasmids encoding the HUH endonuclease, while eukaryotic viruses in the realm likely originated from genetic recombination events that combined DNA from these plasmids with capsid proteins from certain RNA viruses. The prototypic members of Monodnaviria are often referred to as CRESS-DNA viruses, which are associated with a variety of diseases, including those affecting economically important crops and animals. Atypical members, such as papillomaviruses and polyomaviruses, are known to cause various cancers. Members of this realm are also characterized by their frequent integration into host DNA, as well as a relatively high rate of genetic mutations and recombination events.