Intoxication due to anticholinergic burden, exposure to multiple medications with anticholinergic effects, is one of the most common and potentially preventable causes of delirium in the elderly. This paper reviews the basic and clinical literature supporting the ubiquitous nature of this syndrome. Clinical studies in which serum and plasma anticholinergic levels have been measured and correlated with presence and severity of confusional states and delirium are highlighted. They provide the best available support for the anticholinergic hypothesis of delirium. Special emphasis is placed on studies of anticholinergics in patients with Alzheimer disease (AD). Because of the pre-existing cholinergic “lesion” in AD, they may be particularly vulnerable to the effects of anticholinergics. Two recent studies support this, suggesting a deleterious effect on clinical course of AD and possibly on its pathophysiology.