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Combination therapy involving different therapeutic strategies mostly provides more rapid and effective results as compared to monotherapy in diverse areas of clinical practice. The most worldwide famous acetylcholinesterase inhibitor (AChEIs) donepezil for its dominant role in Alzheimer’s disease (AD) has also attracted the attention of many pharmaceuticals due to its promising pharmacological potencies such as neuroprotective, muscle relaxant, and sleep inducer. Recently, a combination of donepezil with other agents has displayed better desirable results in managing several disorders, including the most common Alzheimer’s disease (AD). This study involves all the data regarding the therapeutic effect of donepezil in its combination with other agents and explains its therapeutic targets and mode of action. Furthermore, this review also puts light on the current status of donepezil with other agents in clinical …