While neuropsychoanalysis, as a hybrid discipline, is formally in its third decade of existence, there has been a striking paucity of papers illustrating the clinical applications and relevance of neuroscientific findings for the practicing psychoanalyst. The contributions in this issue illustrate the challenges and possibilities of such an endeavor. Neuroscientific research may strengthen one’s conviction in his/her theoretical orientation, create opportunities for offering ‘neuroscientific interpretations,’ stimulate new ways of thinking or, at its most ambitious, become the basis for a contemporary scientific metapsychology. Maintaining critical thinking, including an awareness of the role of interpretation of scientific facts, is necessary if this interdisciplinary effort is to be productive.