Type 2 diabetes (T2D) is a devastating disease with multiple complications affecting many tissues, most notably the cardiovascular system. To be able to prevent a chronic disease such as T2D, certain requirements have to be met. Knowledge about its natural history with a preclinical phase, modifiable risk factors, effective and simple screening tools to identify high-risk subjects, and effective intervention that is affordable and acceptable are necessary. In addition, the efficacy of the intervention has to be proven under a clinical trial setting. Several major lifestyle intervention trials have been successfully carried out, with consistent results: the risk of T2D in high-risk subjects can be halved, the effect of lifestyle changes is rapid, and benefits are similar in different ethnic groups. Thus, the prevention of T2D is possible in most high-risk subjects, but how to achieve this at the population level remains a major challenge.