With increasing realization of the extent and consequences of depressive comorbidity in epilepsy, much human and animal research has focussed on its explanation. Recent studies tackle all three explanatory possibilities: that epilepsy leads to depression; that depression contributes to causation of epilepsy; or that shared causal factors or processes lead to both epilepsy and depression. These are not mutually exclusive; all three probably contribute. Animal models have provided many insights into the interplay between epilepsy and depressive-like behaviours, both associations and mechanisms. Notably, experimental stress potently affects epilepsy endpoints, as well as depressive-like behaviour, having actions at multiple relevant biological levels. Current general (nonepilepsy) depression modelling is biopsychosocial in nature, integrating insights from genetics, epidemiology, psychology and neurobiology; and takes a lifespan developmental perspective, as the causation of depression is a multistage process with origins in early life - as is the case for many epilepsies. These perspectives need to be more fully adopted in the epilepsy/depression fi eld.