Mastitis is broadly defined as the inflammation of the mammary gland; however, the concept of mastitis is customized to address its social and clinical impact in the case of humans and the health, welfare, and economic consequences for other mammals. There are many microbial, host, and environmental factors that influence the development of mastitis. Some are common to all mammals as well as inherent to each species. Together these factors influence the most prevalent etiological agents for each species and might determine the possibility of interspecies transmission with its consequences to public health. The present review will summarize and compare reports on mastitis etiology and its epidemiology in humans and food animal species.