Enhancement of the activity of cholinergic neurons has been regarded as one of the most promising methods for treating Alzheimer's disease (AD). Donepezil is a representative acetylcholinesterase inhibitor (AChEI) and is a great success among the AChEI drugs. AChEIs are being studied for other mechanisms of action, neuroprotective action, and nicotinic receptor enhancement. AD is a type of neurodegenerative disease and AChEIs have been found to be an effective anti-AD medication. AChEI can alleviate the symptoms and delay the progression of AD, but it cannot cure the disease. However, AChEIs are now the subject of a wide range of clinical studies for other diseases, for example, other types of dementia (such as Lewy body disease, cerebral vascular dementia, and Parkinson's disease dementia), and migraine. These drugs are also being studied as a combination therapy, for example, with an antioxidant, SERM, and NMDA antagonist.