Relevance. 3 agents raccoonpox, skunkpox and volepox belonged to orthopoxviruses of the New World until 2015 years. In last ten-years period skunkpox virus using as vector for creation recombinant vaccines for animals. After 2015 years this group supplemented some more agent primary called virus Alaska, was isolated from ill man. After 2020 years 6 causes of illness by this virus, now named borealpox virus, was registries. Aim. Summary of available information on viruses endemic to the North American continent. Evaluations of еffectivity vaccines on the base virus raccoonpox in laboratory conditions and in Wild World. Monitoring of changes pathogencity virus borealpox by clinical symptoms at infected peoples. Materials. The work uses data from publications posted on the websites of international biomedical research search engines% PubMed, Web of Science, Embase, etc. Results and discussion. Raccoon, skunk and vole smallpox viruses endemic to North America, isolated from their host animals, have specific features that affect their distribution in nature. The high degree of genetic similarity between orthopoxvirus species suggests that rodents may represent the primary ecological reservoir for members of this genus. The most studied representative of the raccoon pox pathogen has an attenuated phenotype and is used as a vector for the creation of vaccine preparations. Based on the construction of a phylogenetic tree, it was found that the orthopoxviruses of the New World are closely related to the orthopoxviruses of the Old World (Eurasia and Africa), and the Alaska virus, capable of infecting humans, forms a separate monophyletic branch. Sequencing of the Alaska virus genome revealed that its closest relative is the Akhmet virus. Human infection with the boreal smallpox virus occurs through contact with small mammals. Conclusion. Analysis of the published data makes it possible to establish that raccoonpox, skunkpox and volepox viruses are not pathogenic to humans. Vaccines on the base virus raccoonpox is immunogenicity and safety for animals and can using as baits. Virus borealpox evoke variola-like disease, proceed in light form at immunedominante peoples. Infected of man by this virus origin by contacts with small mammalians. Study of genomic virus structures all 4 orthopoxviruses of New World allowed conducting their phylogenetic analysis. Established, that raccoonpox, skunkpox and volepox viruses form these parating branch relatively other orthopoxviruses species. Agent of borealpox form the fisting monophyletic branch with localization between orthopoxviruses Old World and New Word, but narrowly related with orthopoxviruses Old World and this relationship execute still on the level of their ancestors.