This contribution seeks to integrate the latest offerings from neuroscience with classical, Kleinian, object relations, and self psychological contributions to the theory of psychosis. I differentiate psychopathology, which has primary psychological meaning, from that which (neurobiologically) originates without psychological meaning. I reinvoke Freud's (1894, 1896) notion of the “actual neuroses” versus the “psychoneuroses” in order to emphasize this distinction. Further, I describe the “black hole” of internal mental space as an invariant phenomenon in psychoses and trace its connection with meaninglessness, which I hold to be the single most important factor in psychotic illness.