Health-related quality of life is becoming the standard measure of personal well-being and human’s health worldwide. Indicators of the population quality of life allow taking into account the subjective incidence, which is often overlooked during routine medical care. In Russia, the health-related quality of life is becoming particularly relevant in connection with the problems of an ageing population, the development of national strategies and programs in the social and healthcare systems, and the increasing prevalence of chronic diseases. The basis of the HRQoL measurement should be based on a proven and reliable methodology that generates comparable estimates of human well-being. Like any complex subjective indicator, HRQoL does not have an unambiguous direct method of measurement. The aim of this paper is a comprehensive description of the methodology for conducting and presenting the results of the study of the HRQoL using the European Quality of Life Questionnaire, EQ–5D. The paper discusses the measurement of HRQoL as a critical component of a modern health care system, describes in detail the administration of HRQoL data using the EQ–5D–3L questionnaire, and provides a methodology for analyzing and presenting the collected data in studies of population and patient health. We address the discussion to clinicians, healthcare providers, and researchers dealing with the problems of studying and measuring the health-related quality of life.