BackgroundMedically unexplained symptoms (MUS) are a common yet challenging encounter in primary care. The aim of this study was to explore how general practitioners (GPs) understand and handle MUS.MethodsThree focus group interviews were conducted with a total of 23 GPs. Participants with varied clinical experience were purposively recruited. The data were analysed thematically, using the concept of framing as an analytical lens.ResultsThe GPs alternated between a biomedical frame, centred on disease, and a biopsychosocial frame, centred on the sick person. Each frame shaped the GPs’ understanding and handling of MUS. The biomedical frame emphasised the lack of objective evidence, problematized subjective patient testimony, and manifested feelings of uncertainty, doubt and powerlessness. This in turn complicated patient handling. In contrast, the biopsychosocial frame emphasised clinical experience, turned patient testimony into a valuable source of information, and manifested feelings of confidence and competence. This in turn made them feel empowered. The GPs with the least experience relied more on the biomedical frame, whereas their more seasoned seniors relied mostly on the biopsychosocial frame.ConclusionThe biopsychosocial frame helps GPs to understand and handle MUS better than the biomedical frame does. Medical students should spend more time learning biopsychosocial medicine, and to integrate the clinical knowledge of their peers with their own.Electronic supplementary materialThe online version of this article (10.1186/s12875-018-0745-2) contains supplementary material, which is available to authorized users.