OBJECTIVE: To synthesise the existing published literature on the perceptions of general practitioners (GPs) or their equivalent on the clinical management of multimorbidity and determine targets for future research that aims to improve clinical care in multimorbidity. DESIGN: Systematic review and metaethnographic synthesis of primary studies that used qualitative methods to explore GPs' experiences of clinical management of multimorbidity or multiple chronic diseases. DATA SOURCES: EMBASE, MEDLINE, CINAHL, PsycInfo, Academic Search Complete, SocIndex, Social Science Full Text and digital theses/online libraries (database inception to September 2012) to identify literature using qualitative methods (focus groups or interviews). REVIEW METHODS: The 7-step metaethnographic approach described by Noblit and Hare, which involves cross-interpretation between studies while preserving the context of the primary data. RESULTS: Of 1805 articles identified, 37 were reviewed in detail and 10 were included, using a total of 275 GPs in 7 different countries. Four areas of difficulty specific to the management of multimorbidity emerged from these papers: disorganisation and fragmentation of healthcare; the inadequacy of guidelines and evidence-based medicine; challenges in delivering patient-centred care; and barriers to shared decision-making. A 'line of argument' was drawn which described GPs' sense of isolation in decision-making for multimorbid patients. CONCLUSIONS: This systematic review shows that the problem areas for GPs in the management of multimorbidity may be classified into four domains. There will be no 'one size fits all' intervention for multimorbidity but these domains may be useful targets to guide the development of interventions that will assist and improve the provision of care to multimorbid patients.