AbstractRecently, in 2022, new cases of human monkeypox virus (hMPXV) occurred in Europe and North America. The first case was reported in Europe in May 2022, and subsequently, more than 50 000 new cases were confirmed in 100 countries. Currently, the classification of hMPXV according to the nextstrain occurs in five big clades (1A, A.1, A.2, A.1.1, and B.1). According to the resurgence of smallpox‐like disease caused by hMPXV and the spread of the virus to the European and American continents, in the present study, we review and summarize the molecular evolution of the hMPXV, determining the molecular evolution of the main clades. A total of 442 hMPXV whole‐genome sequences with available information from the country and sampling date (between October 2017 and 2022), were obtained and evaluated using the Bayesian method. The clade B.1 which is currently circulating was the most frequent (n = 415; 93.9%). The other clades presented the following frequencies: 1A (n = 13; 2.9%), A.1 (n = 10; 2.3%), A.2 (n = 3; 0.7%) and A.1.1 (n = 1; 0.2%) The overall nucleotide divergence of hMPXV was 5.590e‐5. The 1A clade was detected between 2017 and 2020. A.1 was observed, and between 2019 and 2022 some A.2 sequences were detected. In 2022, the great predominance of B.1 was observed. The common ancestor of the hMPXV belongs to the clade 1A and the time to the Most Recent Common Ancestor (tMRCA) was 2017‐04‐04 (Highest Posterior Density 95% (HPD95%): 2017‐03‐09; 2017‐08‐04) on the West African continent. The tMRCA of A.1 was 2018‐05‐21 (HPD95%: 2018‐05‐20; 2018‐07‐04) with divergence of 6.885e‐5 substitutions per site per year. This clade was of West African origin but was eventually detected in European countries. Also, A.2 was detected with sequences of North America and showed tMRCA of 2019‐07‐15 (HPD95%: 2018‐11‐18; 2020‐02‐24). A.1.1 showed tMRCA from 2021 to 06‐05 (HPD95%: 2021‐06‐05; 2021‐11‐26) and this clade was detected in North America and was the precursor for the globally spreading B.1 which tMRCA was 2022‐04‐26 (HPD95%: 2022‐02‐27; 2022‐04‐26). hMPXV has been spread from West Africa to the United Kingdom, Israel, Singapore, the USA, Canada, Portugal, Spain, Ireland, France, Belgium, the Netherlands, Switzerland, Germany, Italy, Slovenia, Austria, the Republic Czech, Sweden, and Finland. hMPXV also reached countries such as Brazil, Mexico, Australia, and Taiwan. The common ancestor of the hMPXV belongs to the clade 1A with origin in the West African continent. Clade B.1 was responsible for the recent widespread worldwide. Immunization to prevent the spread of hMPXV is not yet available to the public, future studies should focus on the development of effective vaccines to contain the spread of this virus.