The mainstay of the pharmacologic management of delirium remains typical antipsychotics, primarily haloperidol. Typical antipsychotics are associated with significant side effects, particularly in the elderly. This article reviews the literature on the use of both typical and atypical antipsychotics in the management of acute delirium, with a focus on the elderly. In this population, typical antipsychotics are associated with substantially more drug induce side effects—either extrapyramidal side effects or anticholinergic effects from the antipsychotics alone or in combination with benztropine or trihexyphenidyl. Anticholinergic toxicity is especially problematic in delirious, demented patients, because most dementias are associated with pre-existing deficiencies in cholinergic neurotransmission. These issues will be reviewed for typical antipsychotics as well as the emerging literature on the use of atypical antipsychotics—risperidone, olanzapine, and quetiapine—for pharmacologic management of acute delirium. Data from two studies conducted at the Wesley Woods Center at Emory University will be briefly reviewed as they constitute the largest series to date investigating the pharmacologic management of delirious demented patients.