Psychiatry enters the new millennium poised to answer many of its central questions. Given the complexity of the human brain and its interactions with our world, these questions are among the most difficult ever addressed by human science. How is the human brain built? How does it change over the life span? What are the precise genetic and environmental risk factors for mental illnesses? What are the pathophysiologic processes that produce the symptoms and disabilities? How do our treatments, including psychotherapy, work? What objective markers can we discover to monitor the progression of the pathogenic processes and the effects of treatment? How will we discover preventive measures and cures that will be effective in diverse populations and settings? Parallel to the pursuit of its public health agenda, psychiatry will grow closer to neuroscience, behavioral science, and neurology. In so doing, those who practice these disciplines will be better positioned to ask meaningful questions about the relationship among mind, brain, and behavior, and to finally overcome the pervasive Cartesianism that continues to incubate stigma and ignorance about mental illness.