Carbohydrates (CHO) can be classified on the basis of their glycemic index (GI), and the use of this classification has been increasingly supported by science. Because of its impact on blood glucose and insulin responses following the ingestion of CHO foods, the GI has been studied in many fields of medicine, including sport nutrition. As a new tool in sport nutrition, glycemic index manipulation has been evaluated to improve the first and second phases of glycogen recovery, glycogen load, and exercise metabolism, including control of rebound hypoglycemia and, it is interesting to note, stimulation of lipid oxidation for longer availability of glucose sources during endurance exercise. Although attractive, the use of GI in sport nutrition has received only partial support from available experimental evidence. At the biochemical level, consistent evidence has been attained to suggest that GI manipulation can determine variations in adipocyte lipolysis, plasma free fatty acids levels, and lipid and CHO oxidation rates during exercise. However, when the effects of GI manipulation have been assessed at the functional level, the results have been inconsistent, with evidence of improved exercise performance in some studies, but not in many others. The purpose of the current article is to review the effects and limits of GI manipulation in sport nutrition, and to propose an overall strategy for its application.