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Background: Multimorbidity is a new concept encompassing all the medical conditions of an individual patient. The concept links into the European definition of family medicine and its core competencies. However, the definition of multimorbidity and its subsequent operationalization are still unclear. The European General Practice Research Network wanted to produce a comprehensive definition of multimorbidity., Method: Systematic review of literature involving eight European General Practice Research Network national teams. The databases searched were PubMed, Embase, and Cochrane (1990-2010). Only articles containing descriptions of multimorbidity criteria were selected for inclusion. The multinational team undertook a methodic data extraction, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines., Results: The team identified 416 documents, selected 68 abstracts, included 54 articles, and found 132 definitions with 1631 different criteria. These criteria were aggregated into 11 themes that led to the following definition: Multimorbidity is defined as any combination of chronic disease with at least one other disease (acute or chronic) or biopsychosocial factor (associated or not) or somatic risk factor. Any biopsychosocial factor, any risk factor, the social network, the burden of diseases, the health care consumption, and the patient's coping strategies may function as modifiers (of the effects of multimorbidity). Multimorbidity may modify the health outcomes and lead to an increased disability or a decreased quality of life or frailty., Conclusion: This study has produced a comprehensive definition of multimorbidity. The resulting improvements in the management of multimorbidity, and its usefulness in long term care and in family medicine, will have to be assessed in future studies., (Copyright © 2013 American Medical Directors Association, Inc. All rights reserved.)