Alzheimer's disease (AD) is turning out to be one o f the lethal diseases in older people. The etiology is multifactorial, and pathophysiology of the disease is complex. Data indicate an exponential rise in the number of case s of AD, emphasizing the need for developing an effective tr eatment. AD also imposes tremendous emotional and f inancial burden to the patient's family and community. The d isease has been studied over a century, but acetylc holinesterase inhibitors is one drugs currently approved for it m anagement. The multitarget approach is based on the unique structural properties of acetylcholinesterase and t he interaction of the enzyme with the inhibitors; w hich could hold the key to treatment of AD in the near future. Posi phen is an experimental AD drug and it lacks acetyl cholinesterase inhibitory activity. Where the objective of this work consists to use th e molecular modeling methods as theoretical approach to study the inhibition of acetylcholinest erase.