Diabetes mellitus is rapidly becoming one of the main health issues in the 21st century. Environmental factors such as lifestyle habits (i.e., physical inactivity and dietary intake) and obesity may act as initiating factors or progression factors for type 2 diabetes. Therefore, changes in lifestyle (i.e., diet and physical activity) should have the potential to postpone or prevent the development of type 2 diabetes mellitus in subjects at high risk (for example, those with impaired glucose tolerance [IGT]). Several independent and well-controlled randomized studies have shown the beneficial impact of a lifestyle intervention program on glucose tolerance, insulin resistance, and diabetes risk in populations at risk for developing type 2 diabetes mellitus. After 2 years of a combined diet and physical activity intervention program, according to general public health guidelines, the Study on Lifestyle-intervention and IGT Maastricht (SLIM) revealed an improved glucose tolerance in the intervention group compared to a further deterioration in the control group. The Finnish Diabetes Prevention Study (DPS) and the US Diabetes Prevention Program (DPP) both observed a 58% reduction in diabetes risk after 3 years of intervention in a high-risk population. Although other intervention strategies can reduce the incidence of diabetes, lifestyle changes are the most effective mean of delaying or preventing the development of type 2 diabetes mellitus. For a successful implementation of a diabetes prevention program in a primary healthcare setting, both patients and healthcare professionals should be aware of the (clinical) significance of impaired glucose tolerance and the effectiveness of lifestyle interventions to prevent or postpone type 2 diabetes mellitus and its complications.