In vitro analyses of the functional properties of neuronal nicotinic acetylcholine receptor (nAChR) disclosed gain of function (i.e. an increase in acetylcholine sensitivity) of mutant receptors associated with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) that may underlie the neuronal network dysfunction responsible for the epileptic seizures. Positron emission tomography (PET) studies in ADNFLE patients suggest a hyperactivation of the cholinergic pathway ascending from the brainstem. An accurate description of the phenotypic aspects of the patients, including precise clinical and electroencephalogram (EEG) semiology of seizures, is mandatory for a correct diagnosis. The most frequent diagnostic dilemma is distinguishing NFLE seizures from parasomnic attacks. An effect of nicotine on the seizures was elegantly demonstrated in a controlled trial and may be explained by considering that the mutant nAChRs are altered and nicotine acts as an acetylcholine receptor agonist.