The review discusses the re-emergence of the Mpox virus (MPXV), a zoonotic disease caused by the Orthopoxvirus genus. MPXV was first identified in monkeys in 1959 and in humans in 1970. It has re-emerged in the U.S. in 2003 and spread globally. Wild African rodents are believed to be the primary reservoir, and the virus can spread through animal trade and international travel. MPXV has two distinct clades, with varying pathogenicity and fatality rates. The smallpox vaccine offers cross-protection against MPXV. Clinical symptoms include fever, muscle pain, and skin lesions. The virus can cause severe illness, particularly in vulnerable populations. Recent outbreaks have led to over 92,783 cases and 171 deaths globally. The review covers the origin, transmission, pathology, diagnosis, and control measures of MPXV. It highlights the need for improved surveillance and immunoprophylactic strategies to prevent and control the spread of the virus. The review also discusses the potential for genetic mutations and recombination to increase the virus's virulence. Vaccines such as JYNNEOS and antiviral drugs like Tecovirimat are available for prevention and treatment. The review emphasizes the importance of continued research and public health efforts to address the ongoing threat of Mpox.The review discusses the re-emergence of the Mpox virus (MPXV), a zoonotic disease caused by the Orthopoxvirus genus. MPXV was first identified in monkeys in 1959 and in humans in 1970. It has re-emerged in the U.S. in 2003 and spread globally. Wild African rodents are believed to be the primary reservoir, and the virus can spread through animal trade and international travel. MPXV has two distinct clades, with varying pathogenicity and fatality rates. The smallpox vaccine offers cross-protection against MPXV. Clinical symptoms include fever, muscle pain, and skin lesions. The virus can cause severe illness, particularly in vulnerable populations. Recent outbreaks have led to over 92,783 cases and 171 deaths globally. The review covers the origin, transmission, pathology, diagnosis, and control measures of MPXV. It highlights the need for improved surveillance and immunoprophylactic strategies to prevent and control the spread of the virus. The review also discusses the potential for genetic mutations and recombination to increase the virus's virulence. Vaccines such as JYNNEOS and antiviral drugs like Tecovirimat are available for prevention and treatment. The review emphasizes the importance of continued research and public health efforts to address the ongoing threat of Mpox.