This entry describes Down syndrome, otherwise known as trisomy 21, from multiple perspectives. The first portrays Down syndrome from a medical point of view and its prevalence today, highlighting the presence of a specific phenotype. In addition, the main milestones in the history of the medical and diagnostic description of Down syndrome are presented, including changes in terminology and the development of invasive prenatal tests first and noninvasive tests later. The implementation of prenatal testing and the change in terminology allow us to understand the prejudices associated with Down syndrome today. The genetic condition associated with trisomy 21 is the most represented and recognized intellectual disability in society, influencing the greater representation of people with Down syndrome in different public spaces and advertising campaigns, without this leading to higher rates of social inclusion or greater support. In some countries social protection or health care systems are insufficient; in others practices persist that fail to respect the human rights of persons with disabilities, included in the United Nations Convention on the Rights of Persons with Disabilities. In some countries, evidence shows that noninvasive prenatal testing has contributed to lower birth rates among the population with Down syndrome. This development has been used as a political argument by pro-life groups seeking to restrict women’s sexual and reproductive rights, underscoring the need to examine the current challenges of Down syndrome through a gender perspective. Finally, the chapter concludes by highlighting the main forms of discrimination faced by women with Down syndrome in different spheres, including higher rates of sexual abuse, lack of gynecological care, and limited employment opportunities.