Beginning with an overview of AD pharmacotherapy and existing blockbuster drugs, this review covers the potential of both natural and synthetic small molecules; the role of cholinesterases in the on-set and progression of AD and their inhibition; the role of BACE-1 in the production of β-amyloid proteins, one of the key reasons of the progression of AD; and other targets identified for AD drug discovery. Here, BCHE is linked to Alzheimer disease.