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Preventive strategies in endocrinology focus on five major fields (the big five): thyroid gland disorders, obesity and diabetes mellitus, dyslipidemia, arterial hypertension and osteoporosis. These highly prevalent conditions have a high morbidity and mortality. As many can be prevented by relatively simple nonpharmacological measures or effectively mitigated by low-threshold pharmacological interventions, they represent model diseases for prevention in internal medicine. This article outlines the current options and discusses them in the context of current prevention strategies. Endocrine and diabetic diseases are among the most common and consequential chronic disorders in industrialized countries and essentially contribute to the total morbidity and mortality. Principal preventive strategies include structural prevention (environmental prevention), such as promoting anti-adipogenic and anti-diabetogenic social structures and behavioral prevention. The emphasis of preventive strategies is on population-related measures, structured screening programs and evidence-based lifestyle interventions. Based on current epidemiological data and guidelines, practical approaches are presented, ranging from iodine prophylaxis, lipid and blood pressure screening to promotion of healthy bone and obesity preventive structures. The concepts discussed demonstrate that effective endocrine and diabetological prevention requires coordinated action across clinical medicine, public health and health policy to realize its full potential.