Acetylcholinesterase inhibitors have demonstrated safety and efficacy in patients with mild to moderate Alzheimer's disease (AD). Although studies of biomarkers in AD suggest a neurobiological rationale for continuing cholinomimetic therapy in patients with severe AD, there have been few studies on the effects of these drugs in such patients. While the interpretation of earlier studies on therapy for severe AD has been complicated by the inclusion of patients with moderate AD, a recent study in Swedish nursing home residents demonstrates the clinical utility of donepezil in a population of exclusively severe patients – i.e. those with Mini-Mental State Examination scores of 1 to 10 inclusive. Significant differences favoring donepezil treatment were observed at the end of this six-month, double-blind placebo-controlled study on the two primary outcome measures: the Severe Impairment Battery (SIB) and Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory for Severe AD (ADCS-ADL-severe). Donepezil-treated patients showed a mean improvement on the SIB after six months compared with baseline, and less decline on the ADCS-ADL-severe than would be expected for untreated patients. These results extend and confirm earlier data suggesting that donepezil is effective in patients with moderate and severe AD.