Wayne Fenton, MD, died on September 3, 2006, while giving emergency clinical care. His leadership at National Institute of Mental Health provided a framework for therapeutic discovery. He crafted a new approach to psychosis based on poor functional outcomes and the psychopathology domains underlying long-term morbidity. His research and clinical observations during his career at the Chestnut Lodge clarified the unmet therapeutic needs in schizophrenia and provided the foundation for his vision. The results have radically changed the paradigm for discovery with emphasis on impaired cognition and negative symptom psychopathology.