Current progress in the cognitive and affective neurosciences affects the development of psychoanalytic theory and practice. However, despite the emerging dialogue between neuroscience and psychoanalysis, the neuronal processes underlying defense mechanisms remain unclear. We consider defense mechanisms as complex emotional-cognitive constellations. As such they require specific functional mechanisms to integrate neuronal activity across several brain regions—that is, neuronal integration. We develop hypotheses about the relationship between principles of neuronal integration and certain defense mechanisms. Neuropsychological and imaging findings in neuropsychiatric disorders are discussed in relation to neuronal integration and specific defense mechanisms. We conclude that the investigation of neuronal integration contributes to revealing the psychophysiological mechanisms underlying defense mechanisms.