Otto Kernberg provides us with a detailed and sophisticated account of how contemporary evidence from neuroscience can be fitted into the ego psychological-framed object relations theory that he has been developing for many years. In this commentary, I frame the clinical lessons to be drawn from this and other neuroscience evidence by considering four questions that every psychoanalyst answers, explicitly or implicitly, whenever they are at work. What is it that is unconscious in a session? What is it that is repeated to produce the problems patients have? What goes on in a session? How can analysis work and what should we communicate to patients? Although knowledge of neurobiology cannot substitute for clear theory about how to conduct psychoanalysis or the need to manage the emotional challenge of adopting a psychanalytically framed disposition, I suggest it can help us to distinguish aspects of theory and practice that do not stand the test of time and so help to clean up and clarify the specificity of psychoanalysis.