Alzheimer’s disease (AD) is the most common type of dementia, more than 100 years ago the alzheimer’s disease was first identified, but research into its risk factors, causes, symptoms, and treatment has gained momentum only in the last 30 years. The cholinesterase inhibitors (ChEIs) were the first anti-Alzheimer drugs approved by the Food and Drug Administration (FDA), by inhibiting acetylcholinesterase these are capable of improving cholinergic neurotransmission. Rivastigmine, galantamine, and donepezil these are the most common ChEIs used to treat cognitive symptoms in mild to moderate AD. In particular, to treat AD patients worldwide the lattermost drug has been widely because it is significantly less hepatotoxic and superior tolerated than its predecessor, tetra hydro amino acridine. It also demonstrates high selectivity towards acetylcholinesterase inhibition and has a long duration of action. For the donepezil these are the formulations available like sustained release (23 mg), immediate release (5 or 10 mg), and orally disintegrating (5 or 10 mg) tablets, all of which are proposed for oral-route administration. Since the oral donepezil therapy is associated with adverse events in the gastrointestinal system and in fluctuations of plasma, an alternative route of administration, such as the transdermal one, has been recently attempted. The goal of this paper is to provide an important overview of AD therapy with donepezil, focusing particularly on the advantages of the transdermal over the oral route of administration.