Religious experience is brain-based, like all human experience. Clues to the neural substrates of religious-numinous experience may be gleaned from temporolimbic epilepsy, near-death experiences, and hallucinogen ingestion. These brain disorders and conditions may produce depersonalization, derealization, ecstasy, a sense of timelessness and spacelessness, and other experiences that foster religious-numinous interpretation. Religious delusions are an important subtype of delusional experience in schizophrenia, and mood-congruent religious delusions are a feature of mania and depression. The authors suggest a limbic marker hypothesis for religious-mystical experience. The temporolimbic system tags certain encounters with external or internal stimuli as depersonalized, derealized, crucially important, harmonious, and/or joyous, prompting comprehension of these experiences within a religious framework.