Human-animal interaction (HAI) refers to the mutual and dynamic relationships between people and animals and the ways in which these interactions may affect physical and psychological health and well-being (McCardle, McCune, Griffin, & Esposito, 2011). The effects described from HAI investigations are often focused largely on the many well-known positive benefits for people: for example, reduction of blood pressure, lower risk of allergies and asthma in children, reduced stress and depression. Historically, few HAI investigations have intentionally focused on or addressed the potential benefits or harm of HAI to the animals involved.The intent of this chapter is to provide a balanced perspective on animal well-being and welfare in the study of HAI and, in the context of this volume, to explore the value of neuroscience as an avenue for discovering the basis of the human-animal bond. Neuroscience may be able to provide explanations for some of the observed effects of HAI, as well as identify the