Acetylcholinesterase inhibitors (AChEIs) have been shown to produce a small, but significant, improvement in cognition in patients with Alzheimer's disease. However, not all patients respond equally, and cognitive benefit may be of limited duration. Although new AChEIs continue to be developed, more recent studies have been aimed at developing inhibitors that have additional actions separate from AChE inhibition. Importantly, new treatments that target the underlying pathogenic mechanism of Alzheimer's disease (statins, secretase inhibitors, vaccination) may eventually emerge. These new treatments could make AChEI therapy less relevant for treatment of Alzheimer's disease.