BACKGROUND: Several systematic reviews evaluating the use of telemedicine by clinicians, patients, and health authorities to improve the delivery of care in the 53 member states of the World Health Organization (WHO) European Region have been conducted in recent years. However, a study summarizing the findings of these reviews has not been conducted. OBJECTIVE: This overview of systematic reviews aimed to summarize findings regarding the use of telemedicine across the 53 member states and identify the medical fields and levels of care in and at which the effectiveness, feasibility, and applicability of telemedicine have been demonstrated. The barriers to and facilitators of telemedicine use were also evaluated and collated to help with the design and implementation of telemedicine interventions. METHODS: Through a comprehensive systematic evaluation of the published and unpublished literature, we extracted clinical, epidemiological, and technology-related data from each review included in the study. We focused on evaluating the barriers to and facilitators of the use of telemedicine apps across the 53 member states considered. We rated the methodological quality of each of the included reviews based on A Measurement Tool to Assess Systematic Review 2 approach and judged the overall certainty of evidence by using the Grading of Recommendations, Assessment, Development, and Evaluations methodology. The entire process was performed by 2 independent authors. RESULTS: This overview drew on data from >2239 primary studies, with >20,000 enrolled patients in total, within the WHO European Region. On the basis of data from randomized trials, observational studies, and economic evaluations from several countries, the results show a clear benefit of telemedicine technologies in the screening, diagnosis, management, treatment, and long-term follow-up of a series of chronic diseases. However, we were unable to pool the results into a reliable numeric parameter because of the high heterogeneity of intervention methodologies, scheduling, primary study design discrepancies, settings, and geographical locations. In addition to the clinical outcomes of the interventions, the social and economic outcomes are highlighted. CONCLUSIONS: The application of telemedicine is well established across countries in the WHO European Region; however, some countries could still benefit from the many uses of these digital solutions. Barriers related to users, technology, and infrastructure were the largest. Conversely, the provision of health services using technological devices was found to significantly enhance patients' clinical outcomes, improve the long-term follow-up of patients by medical professionals, and offer logistical benefits for both patients and health workers. TRIAL REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews) CRD42022309375; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=309375.