The most successful approach for treating people with Alzheimer's disease to date has been by improving cholinergic transmission using cholinesterase inhibitors. Many of these drugs selectively inhibit acetylcholinesterase but some agents inhibit both acetylcholinesterase and butyrylcholinesterase. Recent evidence from studies examining butyrylcholinesterase in post mortem brain samples from dementia patients and examining the relationship between butyrylcholinesterase polymorphisms and the progression of cognitive impairment in dementia with Lewy bodies and Alzheimer's disease add to a body of work suggesting that butyrylcholinesterase is present in key brain areas and may influence the maturation of plaques in Alzheimer's disease. These accumulating data suggest that butyrylcholinesterase contributes to disease progression in people with dementia, which may be particularly important in individuals with more severe dementia as butyrylcholinesterase activity increases with disease development. It is a priority for future clinical trials to determine whether agents which inhibit butyrylcholinesterase and acetylcholinesterase have a greater clinical efficacy.