A review is presented of the scientific literature on the effects of sugars (mono- and disaccharides), when used as tobacco additives, on the formation of acetaldehyde in mainstream (MS) smoke and the potential bioavailablity of MS smoke acetaldehyde derived from sugars to the smoker. The experimental data supports the following conclusions. Sugars, e.g., d-glucose, d-fructose, and sucrose, do not produce greater yields of acetaldehyde in MS smoke than are produced from tobacco itself on a weight-for-weight basis. A variety of studies suggests that natural tobacco polysaccharides, including cellulose, are the primary precursors of acetaldehyde in MS smoke. In a number of different studies using commercial cigarette brands, MS smoke yields of acetaldehyde correlate (r > 0.9) with both MS smoke “tar” and carbon monoxide. MS smoke acetaldehyde yields are affected more by cigarette design characteristics that influence total smoke production, such as filter ventilation, filtration, and paper porosity, than by reducing sugars. MS smoke acetaldehyde deposits primarily in the upper respiratory tract, including the mouth, of the smoker. Acetaldehyde is rapidly metabolized by aldehyde dehydrogenase in the blood and elsewhere in the body, including at the blood−brain barrier. Tobacco sugar-derived MS smoke acetaldehyde from commercial cigarettes is unlikely to result in direct central nervous system effects on the smoker.