In the last century our profession has witnessed extraordinary changes in the knowledge base of psychiatry. As the new millennium begins, we asked several lead researchers what they thought would be the major research questions in psychiatry that should be answered in the 21st century. We also suggested that they consider broad questions that are not necessarily specific to a single psychiatric diagnosis. Both to ensure that their pieces reflect their own views and to diminish censored thought and inhibited writing, we told our panel that their articles would not be peer reviewed. Here are our authors' perspectives on the directions of research in the new millennium.