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Epilepsy is one of the most frequent human neurological diseases. Clinical symptoms of epilepsy are largely confined to the cerebral cortex but, given the scarce data available about the synaptic circuitry of the normal and epileptic human brain, the basic mechanism (or mechanisms) of human seizure activity is still a mystery. This disease can appear after multiple brain pathologies (e.g., tumors, vascular alterations, developmental abnormalities, etc.). However, these alterations are not intrinsically epileptogenic, since some patients displaying them are epileptic, whereas others are not. Thus, it is unknown how and why normal cortical circuits become epileptogenic. In this article, we explain the hypothesis that chandelier cells (which are considered to be the most powerful cortical inhibitory interneuron) may represent a key component in the etiology of epilepsy.