The article discusses the re-emergence of the Mpxv virus (MPXV), which causes zoonotic disease in humans. First reported in monkeys in 1959 and in humans in 1970, MPXV has re-emerged in recent years, spreading globally. Wild African rodents are considered the reservoir of MPXV, and factors such as the exotic animal trade and international travel contribute to its spread. Phylogenetic analysis reveals two clades, with clade I being more virulent. The smallpox vaccine offers cross-protection, but those without prior exposure to Orthopoxvirus are more vulnerable. Clinical manifestations include fever, muscle pain, and skin lesions. As of November 2023, 92,783 cases and 171 deaths have been reported in 116 countries. The article highlights the need for improved surveillance, control measures, and immunomodulation strategies to prevent MPXV transmission. It also covers the virus's origin, transmission, pathology, diagnosis, and treatment options, emphasizing the importance of coordinated efforts among health professionals and scientists to address this global public health concern.The article discusses the re-emergence of the Mpxv virus (MPXV), which causes zoonotic disease in humans. First reported in monkeys in 1959 and in humans in 1970, MPXV has re-emerged in recent years, spreading globally. Wild African rodents are considered the reservoir of MPXV, and factors such as the exotic animal trade and international travel contribute to its spread. Phylogenetic analysis reveals two clades, with clade I being more virulent. The smallpox vaccine offers cross-protection, but those without prior exposure to Orthopoxvirus are more vulnerable. Clinical manifestations include fever, muscle pain, and skin lesions. As of November 2023, 92,783 cases and 171 deaths have been reported in 116 countries. The article highlights the need for improved surveillance, control measures, and immunomodulation strategies to prevent MPXV transmission. It also covers the virus's origin, transmission, pathology, diagnosis, and treatment options, emphasizing the importance of coordinated efforts among health professionals and scientists to address this global public health concern.