In October 2005, UNESCO Member States adopted by acclamation the Universal Declaration on Bioethics and Human Rights. For the first time in the history of bioethics, some 190 countries committed themselves and the international community to respect and apply fundamental ethical principles related to medicine, the life sciences and associated technologies. This publication provides a new impetus to the dissemination of the Declaration, and is part of the organisation’s continuous effort to contribute to the understanding of its principles worldwide. The authors, who were almost all involved in the elaboration of the text of the Declaration, were asked to respond on each article: why was it included; what does it mean; and, how can it be applied. Their responses shed light on the historical background of the text and its evolution throughout the drafting process. They also provide a reflection on its relevance to previous declarations and bioethical literature, and its potential interpretation and application in challenging and complex bioethical debates.