Objective: The cause of mesial temporal lobe epilepsy (MTLE) is often unknown. We ascertained to what extent newly diagnosed nonlesional MTLE actually represents familial MTLE (FMTLE). Methods: We identified all consecutive patients presenting to the Austin Health First Seizure Clinic with MTLE and normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis over a 10-year period. Patients' first-degree relatives and pairwise age- and sex-matched controls underwent a comprehensive epilepsy interview. Each interview transcript was reviewed independently by 2 epileptologists, blinded to relative or control status. Reviewers classified each subject as follows: epilepsy, specifying if MTLE; manifestations suspicious for epilepsy; or unaffected. Physiological déjà vu was noted. Results: Forty-four patients were included. At the Clinic, MTLE had been recognized to be familial in 2 patients only. Among 242 subjects interviewed, MTLE was diagnosed in 9 of 121 relatives versus 0 of 121 controls (p = 0.008). All affected relatives had seizures with intense déjà vu and accompanying features; 6 relatives had not been previously diagnosed. Déjà vu experiences that were suspicious, but not diagnostic, of MTLE occurred in 6 additional relatives versus none of the controls (p = 0.04). Physiological déjà vu was common, and did not differ significantly between relatives and controls. After completing the relatives' interviews, FMTLE was diagnosed in 8 of 44 patients (18.2%). Interpretation: FMTLE accounts for almost one-fifth of newly diagnosed nonlesional MTLE, and it is largely unrecognized without direct questioning of relatives. Relatives of patients with MTLE may experience déjà vu phenomena that clinically lie in the “borderland” between epileptic seizures and physiological déjà vu. Ann Neurol 2017;82:166–176.