The 'Research Agenda for General Practice/Family Medicine and Primary Health Care in Europe ' summarizes the evidence relating to the core competencies and characteristics of the Wonca Europe defi nition of GP/ FM, and its implications for general practitioners/ family doctors, researchers and policy makers. The European Journal of General Practice publishes a series of articles based on this document. The previous articles presented background, objectives, and methodology, as well results on 'primary care management ' and 'community orientation ' and the person-related core competencies of GP/ FM. This article refl ects on the general practitioner ' s 'specifi c problem solving skills '. These include decision making on diagnosis and therapy of specifi c diseases, accounting for the properties of primary care, but also research questions related to quality management and resource use, shared decision making, or professional education and development. Clinical research covers most specifi c diseases, but often lacks pragmatism and primary care relevance. Quality management is a stronghold of GP/ FM research. Educational interventions can be effective when well designed for a specifi c setting and situation. However, their message that 'usual care ' by general practitioners is insuffi cient may be problematic. GP and their patients need more research into diagnostic reasoning with a step-wise approach to increase predictive values in a setting characterized by uncertainty and low prevalence of specifi c diseases. Pragmatic comparative effectiveness studies of new and established drugs or non-pharmaceutical therapy are needed. Multi-morbidity and complexity should be addressed. Studies on therapy, communication strategies and educational interventions should consider impact on health and sustainability of effects.