There is increasing evidence that epileptic activity involves widespread brain networks rather than single sources. Using high-density Electroencephalography (EEG), Electrical Source Imaging (ESI) and Granger-causality measures, we investigated whole-brain directed functional connectivity in left and right Temporal lobe Epilepsy (LTLE and RTLE, respectively), during interictal spikes and spike-free epochs, and in healthy subjects. This allowed us to identify the main drivers and connectivity patterns of interictal epileptic activity in TLE, and of the resting-state in both TLE and healthy subjects. We further found that LTLE and RTLE had different interictal network patterns, and that resting-state outflows were decreased and had a different pattern in TLE vs healthy controls. Our studies show that whole-brain EEG-based directed functional connectivity analysis is a very promising tool to investigate how brain regions driver others during epileptic and non-epileptic activity. This could importantly contribute for epilepsy presurgical planning, especially in patients whose focus is not clear by other already available neuroimaging tools.