To our knowledge, this is the first reported human study that evaluated the effect of daily dietary supplementation with bioactives in blueberries on whole-body insulin sensitivity in obese, nondiabetic, and insulin-resistant men and women. The uniqueness of this study relates to the design, which was randomized, double blinded, and placebo controlled. By design, the blueberry and placebo smoothies were identical in physical appearance and macronutrient content with the exception of adding the blueberry bioactives to the blueberry smoothie. Another strength of the study was the use of the most precise metabolic technique for assessing whole-body insulin sensitivity, i.e., hyperinsulinemic-euglycemic clamps. The major finding was that daily consumption of whole blueberry bioactives for 6 wk improved insulin sensitivity in a population at high risk for type 2 diabetes compared with ad libitum dietary intake alone.