Children with epilepsy are affected by several factors, including clinical and social variables, which can lead to reductions in quality of life (QOL). Among these variables, factors relating to seizure severity such as frequent seizures and status epilepticus (SE) have been identified as important predictors of QOL. In addition, frequency of interictal epileptiform discharges (IEDs) on the electroencephalogram (EEG) may also lead to cognitive declines and behavioral disturbances. Moreover, frequent seizures and/or IEDs may play a role in emotional mediators such as stigma and fatigue in childhood epilepsy. Seizure severity and/or IEDs are thus important QOL-related factors in childhood epilepsy. Frontal lobe dysfunctions such as cognitive decline and behavioral disturbances can result in reduced QOL for both the child and their family. Frontal and prefrontal lobe growth disturbances can be present during active-phase epilepsy in some children with neuropsychological impairments. Recovery from prefrontal lobe growth disturbance may depend on the active seizure period. Disturbance of prefrontal lobe growth can recover more rapidly in children with a shorter active seizure period. In contrast, recovery may be delayed in children with a longer active seizure period. Accordingly, severe seizures can lead to neuropsychological impairments in association with prefrontal lobe growth disturbance in children with epilepsy. Moreover, frequent seizures can lead to having seizure-associated headache, perception of self-stigma and parental stigma, and fatigue. In addition, IEDs on EEG, representing persistent pathological neuronal discharges, may be associated with several pathological aspects. Frontal IEDs can be a risk factor for recurrent seizures, cognitive decline, and behavioral disturbances and may also play a role as an emotional mediator similar to stigma. In addition, behavioral disturbances may result in the presence of secondary bilateral synchrony (SBS) on EEG. Behavioral disturbances can be improved in association with reduction of IEDs in children with frontal IED and SBS. Seizure severity and IEDs on EEG may thus be associated with neuropsychological impairments, leading to QOL reduction. Therapeutic management may be desirable to remit seizures and EEG abnormalities such as frontal IED and SBS as soon as possible to improve QOL in children with epilepsy.