Orf virus (ORFV) is an epitheliotropic, double-stranded DNA pathogen belonging to the genus Parapoxvirus, and it is the causative agent of contagious ecthyma (CE) in small ruminants. It is an endemic disease on goat and sheep herds around the world. It is often a neglected disease, with impacts on herd health and productivity, while also being an occupational zoonosis. This review explores the causative agent of ovine ecthyma, its epidemiology, and clinical manifestations, with a particular emphasis on its interaction with the host's immune system and the development of ORFV vaccines. Like other members of the Poxviridae family, ORFV expresses numerous immunomodulatory genes, which complicate vaccination efforts and disease management. This review highlights the challenges posed by ORFV in achieving effective immunization and discusses potential vaccine strategies to overcome these obstacles.