Labels serve as identifiers and convenient descriptors of inanimate and animate objects. In humans, given labels can easily become part of an individual’s self-perceived identity. Negative labels ascribed to a person can result ininternalized stigma, a state that will shape the subject’s biography. This can ultimately impact the person’s mental and physical health sinceperceivedand/oranticipated stigmadiscourages the use of social and health services. Per definition, stigma involves labeling of persons with physical, mental, or social characteristics that do not match the observer’s arbitrarily conditioned and calibrated sense of norms (public stigma); such labeling may eventually become embedded in rules, regulations, and laws (structural stigma). Internalized stigma projects onto a person’s emotions and actions.Public (enacted) stigmaresults from stereotyping (collectively agreed-upon notions about a group of persons that are used to categorize these people) and devaluation, which subsequently leads to social distancing, discrimination, and blatant abuse of human rights. Much of what we know about stigma results from research in the psychosocial sciences and, more recently, from social neuroscience. The stigma around mental health has generated much attention in the field of psychiatry where, to date, most research has focussed on epidemiology and anti-stigma interventions. This essay intends to stimulate thought, debate, and research within the behavioral neuroscience community and, therefore, to inform evidence-based design and implementation of neuroscience-based approaches by other professionals working towards the elimination of the stigma attached to mental illness. The article starts by considering the concept of stigma and the psychological processes that give rise to the phenomenon; it also considers how projected and perceived stigma are multiplied. Finally, after a brief review of the few existing neuroscientific explorations of stigma, gaps in our knowledge of the neurobiological basis of stigma are identified and discussed.