Varenicline is an orally administered alpha(4)beta(2) nicotinic acetylcholine (Ach) receptor, partial agonist. This drug has been known to be more effective in the treatment of nicotine withdrawal than bupropion and nicotine replacement therapies. Besides this effectiveness, it has some systemic and neuropsychiatric side effects that physicians have been experienced often. Here, we aimed to draw attention to the possible neuropsychiatric risks of varenicline use by discussing the symptoms, clinical course, and treatment methods of four patients who admitted to psychiatry and neurology outpatient clinics, had a history of the therapeutic dose of varenicline use, and developed neuropsychiatric side effects. The first case was about a panic attack, and the second case had headaches, sleepiness, and tremors. In the third case, a psychotic attack due to varenicline was observed while and in the last case, myoclonic seizure symptoms were seen. Little is known about neuropsychiatric side effects due to varenicline. Neurological and psychiatric side effects should be closely monitored, and patients should be evaluated in a multidisciplinary way. The patients in this study will help to better define the neuropsychiatric side effects due to varenicline.