Deaths in custody warrant scrutiny, not only because they might be due to torture, abuse and inadequate medical care, but also because they pose challenges for detaining authorities. It is a widely overlooked problem that in many prisons deaths are frequent and most of them are considered ‘normal' or ‘natural' and not necessarily investigated while some of them were preventable. The lack of guidance to health care workers or international personnel in the field as to how to proceed in cases of deaths in custody is one of the reasons why investigations into deaths in custody are not conducted or are ineffective. In light of this real and persistent problem, a multidisciplinary research project on the legal, medical and forensic aspects of investigating deaths in custody has been carried out between 2008 and 2013 by the University Centre for Legal Medicine of Geneva and Lausanne, the Geneva Academy of International Humanitarian Law and Human Rights, the University of Bern, the International Centre for Prison Studies (King's College London) and the ICRC. As a result of this collaborative effort, the Guidelines for investigating deaths in custody have been published by the ICRC in 2013. The latter Guidelines fill an important gap by offering practical guidance to detaining authorities, investigating authorities, humanitarian agencies and others on the standards and procedures to be followed when a death occurs in custody. This chapter presents the background, content and usefulness of the Guidelines after having discussed some of the key medical and legal issues related to death in custody such as: how to define deaths in custody? What are the most prevalent causes of deaths in custody? What is the legal framework pertaining to the prevention and investigation of deaths in custody? How to investigate and prevent deaths in custody?