Background: Misophonia is a recently identified condition in which a person perceives a subtle stimulus (e.g., eating sounds, hair twirling) and has an intense, negative emotional response. Misophonia cannot be classified with established nosological systems. Methods: We present a novel five-phase model of misophonia from a cognitive-behavioral framework. This model identifies a learned reflex of the autonomic nervous system as the primary etiology and maintenance of misophonia. Phase one is anticipatory anxiety and avoidance. Phase two is a conditioned physical reflex (for example, the tensing of calf muscles) that develops through stimulus-response Pavlovian conditioning. Phase three includes intense negative emotional responses and accompanying physiological distress, thoughts, urges, and emotion-driven behavior. Phase four is the individual’s coping responses to emotional distress, and phase five is the environmental response and resulting internal and external consequences of the coping behaviors. Each phase helps explain the maintenance of the response and the individual’s impairment. Results: Anticipatory anxiety and avoidance of phase one contributes to an increased arousal and awareness of triggers, resulting in increased severity of the trigger experience. Both the Pavlovian-conditioned physical reflex of phase two and the emotion-driven behavior caused by the conditioned emotional response of phase three increase with in vivo exposure to triggers. Phase four includes internal and external coping behaviors to the intense emotions and distress, and phase 5 includes the consequences of those behaviors. Internal consequences include beliefs and new emotions based on environmental responses to anger and panic. For example, the development of emotions such as shame and guilt, and beliefs regarding how ‘intolerable’ the trigger is. Conclusions: We assert misophonia is a multi-sensory condition and includes anticipatory anxiety, conditioned physical reflexes, intense emotional and physical distress, subsequent internal and external responses, and environmental consequences.