The systemic inflammatory response represents a coordinated set of physiologic actions that serve to fight infection, heal wounds, and promote recovery from external stressors. Thus, under most circumstances an intact systemic inflammatory response increases the likelihood of a successful outcome following acute injury or infection. However, under certain conditions, such as in major trauma, an excessive pro-inflammatory response may arise that worsens the prognosis. Conversely, protein calorie malnutrition can result in immunodeficiency, leaving the individual at risk of infection. Finally, low-grade chronic inflammation that is persistent, as can be seen in obesity, diabetes, and the metabolic syndrome, can lead to serious health risks. Thus, inflammatory states within a range from chronic low-grade to acute severe responses can have profound effects on morbidity and manifest an increased risk of mortality. Therapies to down-regulate the systemic inflammatory response by targeting the source of inflammation may dramatically improve patient outcome in chronic inflammatory states and some acute inflammatory conditions.