Freud lived in a time when technology was incapable of explaining the biological correlates of the mental processes he described in psychoanalytic theory. During the last two decades, advances in neuroimaging methods and neuroscience have provided new insights for understanding mind-brain collaboration. Neurobiological underpinnings of psychoanalytical concepts have been an area of interest in recent years. This paper will suggest a new hypothesis for neurobiology of repression. This hypothesis will be discussed with the help of our knowledge about neurobiological mechanisms underlying perception of the emotional significance of an event, memory formation of an emotionally arousing stimulus, role of prefrontal cortex in modulation of subcortical information, neural mechanisms of suppression and molecular mechanisms of memory erasure. We suggest that dorsolateral prefrontal cortex, and especially its caudal part plays a major role for repression of childhood traumatic events. Possible molecular mechanism of memory erasure in repression is long term depression of glutamatergic neurotransmission between prefrontal cortex- thalamus- limbic system.