Purpose of Review <p>Alzheimer’s disease is a neurological condition that is characterised by different lesions, primarily the senile/neuritic plaques and neurofibrillary tangles. Due to the extensive degradation of cholinergic neurons throughout the hippocampus and cortex, the cholinergic transmission is reduced, which ultimately leads to cognitive abnormalities. As they are heavily influenced by the cholinesterases, cholinesterase inhibitors are the verified group of drugs approved for the disease. This review tries to explore and understand the underlying factors for the positive and negative effects of donepezil.</p> Recent Findings <p>Donepezil, being a reversible, selective, and competitive inhibitor of acetylcholinesterase, significantly stimulates the cholinergic transmission. It has improved performance in several pharmacological models of learning and memory impairments. Numerous extensive studies have confirmed the effectiveness of donepezil in treating symptoms in mild, moderate, and even severe stages of AD based on the patient’s behaviour, daily activities, and cognitive performance. Even though it is used to treat an extensive array of patients suffering from AD, there are some side effects, such as vomiting, diarrhoea, insomnia, convulsions, and bradycardia that may occur with the treatment.</p> Summary <p>Therefore, if the patient is cognitively responding to the drug, other factors, including the presence of other concurrent medications, the dose of the drug needs to be investigated as possible reasons for these adverse events. Hence, to have a better understanding of the complex interplay between donepezil and other factors that can cause these effects, further clinical studies are required to appreciate the positive effects while minimizing the negative ones. </p>