Clinical registries are health information systems, which have the mission to collect multidimensional real-world data over the long term, and to generate relevant information and actionable knowledge to address current serious healthcare problems.This article provides an overview of clinical registries and their relevant stakeholders, focussing on registry structure and functioning, each stakeholder's specific interests, and on their involvement in the registry's information input and output.Stakeholders of clinical registries include the patients, healthcare providers (professionals and facilities), financiers (government, insurance companies), public health and regulatory agencies, industry, the research community and the media.The article discusses (1) challenges in stakeholder interaction and how to strengthen the central role of the patient, (2) the importance of adding cost reporting to enable informed value choices, and (3) the need for proof of clinical and public health utility of registries.In its best form, a registry is a mission-driven, independent stakeholder-registry team collaboration that enables rapid, transparent and open-access knowledge generation and dissemination. Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180077.