For 40 years the General Clinical Research Centers (GCRCs) have provided the infrastructure in Academic Medical Centers (AMCs) in the United States, which enabled and facilitated the extraordinary achievements of twentieth century patient-oriented research. The GCRC program in the United States represents a central theme linking molecular and clinical research directed at elucidating mechanisms of human disease. The GCRC can provide the necessary infrastructure and critical intellectual mass to reach a deeper understanding of human biology and to bring better health to persons in both developed and developing countries. A well-organized GCRC program should encompass educational as well as scientific components. It must be developed with an appropriate quality control infrastructure to provide physician-scientists a broad base of training in ethical principles in conduct of research and in scientific design and modern technology. The Human Genome Project has brought unprecedented opportunities to clinical investigators, but taking full advantage of them will require a rebirth of the GCRC as a program capitalizing on local strengths and differences, a more multicentric program, and a program reaching outside the GCRC walls, beyond institutional walls, and into the community. The GCRCs can appropriately be the clinical arm of the human genome project, harnessing the genetic revolution for human health. The GCRC model can provide a conceptual base on which new international patient-oriented research infrastructures can develop.