Sugars may be Mother Nature’s most essential nutrient since, in the course of evolution, humans have retained the ability to synthesize every sugar needed for metabolic functions while, at the same time, humans lost the ability to make nine amino acids and two fatty acids required for life. During the same evolutionary period, Mother Nature iterated to preferring glucose as the almost sole fuel of the brain and the fetus. Human infants are born with sweet taste receptors and sugars constitutes approximately one-third of the energy supply of human milk. Moreover, complex carbohydrates, half or more of the energy content of human diets, are assimilated only after being broken down to simple sugars whose absorption is enhanced by other fuels serving as the energy source for enterocyte metabolism. If sugars are as unhealthful as many postulate, has Mother Nature been trying to fool us all these eons? More recently, observational studies that cannot prove cause and effect and in which one cannot control correlation interdependencies among the huge number of “exposome” variables, detrimental associations of sugar consumption have been reported repeatedly. Nonetheless, authoritative committee assessments of sugar interventional trials that have controlled for total energy consumption have failed to confirm detrimental effects of sugar consumption, per se.