Neuroscience indicates that 'repetition' is fundamental to brain function. The brain non-consciously predicts what is most likely to happen and sets in motion perceptions, emotions, behaviors and interpersonal responses best adapted to what is expected-before events occur. Predictions enable individuals to be ready 'ahead of time' so reactions occur rapidly and smoothly when events occur. The brain uses past learning as the guide for what to expect in the future. Because of prediction, present experience and responses are shaped by the past. Predictions from early life can be deeply encoded and enduring. Predictions based on the past allow for more efficient brain function in the present, but can lead to mistakes. When what is predicted does not occur, consciousness can be engaged to monitor and correct the situation. But if a perception or emotion seems reasonable for the situation, a person might not notice an error, and a maladaptive 'repetition' may remain unchanged. The author discusses how predictions contribute to psychological defenses and transference repetition, and how conscious self-reflection facilitates therapeutic change. The neuroscience of prediction indicates why, in certain cases, active engagement by the analyst may be necessary. The author makes the argument for use of a 'neuroscience interpretation'.