In the severe stages of Alzheimer's disease, functional autonomy is lost, psychiatric and behavioral symptoms become increasingly troublesome, and cognitive deficits increase until most patients require complete care, usually in specialized nursing homes. Consequently,some health care professionals question the benefits of pharmacologic intervention during these later stages. Since primary care physicians are often first to see these patients, they have key roles in recognizing the benefits of treatment and initiating appropriate management and referral. Three prospective randomized clinical trials of donepezil in severe Alzheimer's disease have been conducted; these show donepezil treatment is associated with functional and cognitive benefits, although behavioral benefits were not consistently observed. Donepezil was well tolerated; side effects were transient, mild to moderately severe, and cholinergic in nature. Donepezil has strong data throughout the Alzheimer's disease spectrum and, therefore, represents a first-line monotherapy that can provide benefits to patients in all stages of Alzheimer's disease.