Lifestyle interventions are reported to reduce the risk of type 2 diabetes in high-risk individuals after mid- and long-term follow-up. Information on determinants of intervention outcome and adherence and the mechanisms underlying diabetes progression are valuable for a more targeted implementation. Weight loss seems a major determinant of diabetes risk reduction, whereas physical activity and dietary composition may contribute independently. Body composition and genetic variation may also affect the response to intervention. Lifestyle interventions are cost-effective and should be optimized to increase adherence and compliance, especially for individuals in the high-risk group with a low socioeconomic status, so that public health policy can introduce targeted implementation programs nationwide. The aims of this review are to summarize the mid- and long-term effects of lifestyle interventions on impaired glucose tolerance and type 2 diabetes mellitus and to provide determinants of intervention outcome and adherence, which can be used for future implementation of lifestyle interventions.