Ecthyma contagiosum, also called contagious pustular dermatosis, is a zoonotic disease caused by the orf virus (OrfV). As a member of the poxviridae family and parapoxvirus genus, this dermatotropic virus has developed an array of mechanisms by which to evade the host immune system in both humans and animals. The ubiquitousness of this pathogen in sheep, goats, and deer has led to the development of orf in diverse areas around the world. Human disease occurs via direct contact with infected animals or fomites. Rarely, human-to-human transmission has been reported. The disease progresses through six clinically distinct dermatologic stages and lesions usually heal in three to six weeks without scarring. Farmers, veterinarians, and hunters represent high-risk groups, as their repeated contact with livestock and wild animals predisposes them to infection. With an increasing number of cattle, livestock, and wild animals being kept as pets, human orf may become more prevalent in the future. Taken with the lack of a widely accepted and successful antiviral treatment regimen, this demonstrates the importance of conducting additional research to further elucidate the pathogenic effects of the OrfV in humans. J Drugs Dermatol. 2017;16(7):684-689.