This chapter reviews randomized clinical trials of the prevention of type 2 diabetes, from small early trials of drugs available in the 1960s to more recent studies, some very large, of additional drugs and of lifestyle interventions designed to produce weight loss and increase physical activity. Most studies show that type 2 diabetes can be prevented or delayed to varying extents by a variety of drugs used to treat type 2 diabetes and by lifestyle interventions. Whether these interventions affect only hyperglycemia during the time the interventions are provided or also affect other health outcomes, such as mortality rates and the development of diabetes complications, is largely unknown.