Under the European Directive on the application of patients' rights in cross-border health care, the development of European reference networks was promoted as one of the prime areas for cross-border cooperation among Member States. These networks are meant to improve access to and provision of high-quality health care to all patients who have conditions requiring a concentration of specialized resources or expertise. At the same time they could act as focal points for medical training and research, information dissemination and evaluation, especially for rare diseases. The idea of pooling resources in order to better address medical conditions that are rare or require very specialized expertise or equipment, corresponds with moves towards concentration of specialized health care services, often motivated by common health systems challenges like tightening financial constraints, workforce shortages and growing attention for quality and safety.This book examines the different ways in which the concept of reference networks has been implemented in European countries, and what kind of medical conditions or interventions it covers in various countries. It also looks at the motivations behind the establishment of such networks, the regulatory and administrative processes for identifying and designating them, as well as the financial arrangements needed for their proper functioning. This study outlines the key policy implications and challenges for developing the concept of reference networks at national and European levels. Ultimately we aim to provide a better understanding of the issues that may be encountered when implementing the Directive.