Severe sepsis remains both an important clinical challenge and an economic burden in intensive care. An estimated 750,000 cases occur each year in the US alone (300 cases per 100,000 population). Lower numbers are estimated for most European countries (e.g. Germany and Austria: 54-116 cases per year per 100,000). Sepsis patients are generally treated in intensive care units (ICUs) where close supervision and intensive care treatment by a competent team with adequate equipment can be provided. Staffing costs represent from 40% to >60% of the total ICU budget. Because of the high proportion of fixed costs in ICU treatment, the total cost of ICU care is mainly dependent on the length of ICU stay (ICU-LOS). The average total cost per ICU day is estimated at approximately 1200 Euro for countries with a highly developed healthcare system (based on various studies conducted between 1989 and 2001 and converted at 2003 currency rates). Patients with infections and severe sepsis require a prolonged ICU-LOS, resulting in higher costs of treatment compared with other ICU patients. US cost-of-illness studies focusing on direct costs per sepsis patient have yielded estimates of 34,000 Euro, whereas European studies have given lower cost estimates, ranging from 23,000 Euro to 29,000 Euro. Direct costs, however, make up only about 20-30% of the cost of illness of severe sepsis. Indirect costs associated with severe sepsis account for 70-80% of costs and arise mainly from productivity losses due to mortality. Because of increasing healthcare cost pressures worldwide, economic issues have become important for the introduction of new innovations. This is evident when introducing new biotechnology products, such as drotrecogin-alpha (activated protein C), into specific therapy for severe sepsis. Data so far suggest that when drotrecogin-alpha treatment is targeted to those patients most likely to achieve the greatest benefit, the drug is cost effective by the standards of other well accepted life-saving interventions.