This document provides justification for the Fiscal Year 2009 research activities of the National Institute of General Medical Sciences, a component of the National Institutes of Health in the U.S. Department of Health and Human Services. NIGMS supports research that answers major questions about life, such as how cells live and die, how cells talk to each other, and how genes and proteins work. Other NIGMS studies focus on the way the body uses energy and how it responds to medicines. This research forms the foundation for new and better ways to diagnose, treat, cure, and prevent disease.