Simple SummaryAnimal-assisted interventions (AAI)s are planned activities carried out in multidisciplinary teams with educational, therapeutic, and ludic-recreational purposes. The multidisciplinary and integrated character identifies AAIs as the expression of one health. While AAIs offer many advantages to subjects, they could be exposed to several zoonotic-pathogens transmissions. Therefore, positive animal welfare, as preventive medicine to avoid accidents or zoonotic transmissions, is a relevant aspect with implications for human and animal health and welfare. The knowledge of several pathogens causing zoonoses in the animal species employed during the AAIs, as well as the preventive measures aimed at reducing and/or preventing the risk, guarantee their safety for patients. This review defines the future outcomes of the AAIs including the strengthening of preventive measures according to a “One Health approach”, the training of the personnel involved in AAIs, and the standardized protocols for hygiene–health–behavioral monitoring, aimed at a future production of health and behavioral certifications.AbstractAnimal-assisted interventions (AAI)s represent the expression of integrated medicine, according to the One Health approach. Actually, animal-assisted therapies and animal-assisted activities are implemented in hospitals, rehabilitation centers, etc. The efficacy of AAIs is based on interspecific interactions and would be impacted by different factors, such as the characters of both the animal and the handler, a suitable selection of animal species, an appropriate animal educational protocol, the relationship between the handler and the animal, and mutual relationship among the animal, the patients, and members of the working team. AAIs produce many advantages for the patients but could expose them to zoonotic-pathogens transmission. Therefore, positive animal welfare, as preventative medicine to avoid incidents or transmission of zoonosis, is a relevant aspect with implications for human and animal health and wellbeing. This review aims to summarize the current published knowledge regarding the occurrence of pathogens in AAIs and to discuss their relevance in light of health and safety in AAIs participants. In addition, this review will contribute to defining the state of the art of AAIs through a careful benefits/challenges analysis and offers discussion points on the possible future developments according to the One Health approach.