Sepsis continues to pose a clear challenge as one of the most difficult and costly problems to treat and prevent. Sepsis is caused by systemic or localized infections that damage the integrity of microcirculation in multiple organs. The challenge of sepsis and its long-term sequelae was addressed by the National Institutes of Health National Heart Lung and Blood Institute Division of Blood Diseases and Resources. Defining sepsis as severe endothelial dysfunction syndrome that causes multiorgan failure in response to intravascular or extravascular microbial agents, the National Heart Lung and Blood Institute panel proposed the concept of genome wars as a platform for new diagnostic, therapeutic, and preventive approaches to sepsis.