Orf virus (ORFV) is the etiologic agent of Orf or ecthyma contagiosum in humans but primarily affects different domestic and wild animals. The disease mostly affects sheep, goats and other small wild ruminants and spreads to humans through direct contact with infected animals or by way of contaminated fomites worldwide. ORFV is taxonomically classified as a member of the genus Parapoxvirus. It is known to have tolerance to inactivation in a drier environment, and it has been recovered from crusts after several months to years. Among immunocompetent people, the lesions usually resolve by its natural course within a maximum of 8 weeks. In immunosuppressed patients, however, it needs the use of various approaches including antiviral, immune modifier or minor surgical excisions. The virus through its association with divergent host ranges helps to develop a mechanism to evade the immune system. The relative emergence of Orf, diagnosed on clinical ground among human cases, in unusual frequencies in southwest Ethiopia between October 2019 and May 2020, was the driver to write this review. The objective was to increase health care providers' diagnostic curiosity and to bring the attentiveness of public health advisors for prevention, control and the development of schemes for surveillance of Orf zoonosis in a similar setting like Ethiopia.