Elucidation of the association of tobacco and alcohol use with Alzheimer's disease (AD) may advance etiological hypotheses and provide a theoretical basis for treatment. There is currently no cure or effective treatment for AD, and no cause has been established. Pharmacological evidence supports a plausible biological mechanism for the involvement of tobacco use: nicotine compensates for some of the cholinergic deficits observed in AD. Epidemiological evidence, however, is inconsistent, although recent meta-analyses also support a protective effect. Although smoking per se is certainly not advocated, further investigation of a potential protective effect of nicotine on AD is warranted. Pharmacological studies implicate alcohol use as a possible risk factor for AD; the epidemiological studies are again inconclusive. Alcohol consumption is associated with daily smoking and smokers are, in turn, more likely to consume alcohol. Since tobacco use may decrease the risk of developing AD and alcohol use may increase it, it is important to consider these two substances together: the effect of one may negate the other. This literature review critically evaluates the evidence for an association of tobacco and alcohol use with AD and identifies key issues for further research.