Interictal spiking is seen in the EEG of epileptic patients between seizures. To date, the roles played by interictal events in seizure occurrence and in epileptogenesis remain elusive. While interictal spikes may herald the onset of electrographic seizures, experimental data indicate that hippocampus-driven interictal events prevent seizure precipitation. Even less clear than the role of interictal events in seizure occurrence is whether and how interictal spikes contribute to epileptogenesis. Thus, while plastic changes within limbic neuronal networks may result from ongoing interictal activity, experimental evidence supports the view that epileptogenesis is accompanied by a decrease in hippocampus-driven interictal activity.