In modern times, the determination of the epileptogenic zone demands a sophisticated combination of neurophysiological and neuroimaging tools. Historically however, the concept of the epileptogenic zone was based on and has evolved from the recording of interictal spikes, both in the scalp electroencephalogram (EEG) and, particularly, in the acute electrocorticogram (ECoG). Because the role of interictal spikes is still not always clear in the decision-making process of epilepsy surgery, the relevance of these spikes in the definition of the epileptogenic zone is reviewed here, starting with the pioneering work of the Montreal school.