The burden of disease in the United States is high. Mental illness is currently the leading cause of disease burden among 15- to 44-year-olds. This phenomenon is occurring despite the many advances that have been made in clinical research. Several efficacious interventions are available to treat many of these disorders; however, they are greatly underutilized within community settings. Achievements in basic science such as the completion of the Human Genome project have provided access to the examination of the neurobiology of mental disorders. To address the overall burden of disease, a reengineering of clinical science must take place. Adopting a translational framework will capitalize on the synergy of integrating basic science and clinical knowledge to inform real-world practices. This article will define and discuss translational research and the current National Institutes of Health initiatives that have been developed to support its implementation.