Epileptogenesis describes the mechanisms of how epilepsies are generated. We have chosen four areas in which significant progress has been achieved in understanding epileptogenesis. Those are (1) inflammatory processes which play an increasingly important role for the generation of temporal lobe epilepsy with hippocampal sclerosis (TLE with HS), (2) disturbances of intrinsic properties of neuronal compartments, in particular acquired defects of ion channels of which those in dendrites are described here for TLE with HS, (3) epigenetic effects, which affect for example the methylation of promoters and secondarily can change the expression of specific genes in TLE with HS, and finally (4) the epileptogenesis of idiopathic epilepsies which are caused by inborn genetic alterations affecting mainly ion channels. Apart from aspects of basic research, we will describe clinical consequences and therapeutic perspectives.