Severe sepsis and septic shock represent challenging problems for the health care system. Despite adequate antibiotics and modern intensive care, severe sepsis is associated with a substantial mortality rate of around 30%, which rises even higher if exacerbated by septic shock, and the incidence continues to increase. In severe sepsis and septic shock, the normally tightly controlled balance between the inflammatory, coagulatory and neuroendocrine systems is lost. Our understanding of the causes, mitigating factors and mediators of severe sepsis has advanced in the last number of years. However, immunomodulatory interventions specifically directed against cytokines that all appeared promising in animal studies, did not translate well into human clinical trials. It has been suggested that the failure of many sepsis trials may in part be due to enrollment of diverse patients with sepsis of varying severity and different causative microorganisms. We, and others, believe that successful clinicaltrials of immunotherapeutic agents in sepsis require well defined patient cohorts with respect to severity and microbiological aetiology. This thesis project aimed to document clinical presentation and outcome of severe sepsis and septic shock, to evaluate clinical efficacy of adjunctive polyspecific intravenous immunoglobulin therapy (IVIG) in streptococcal toxic shock syndrome (STSS) and to define pathogenic mechanisms in sepsis, with a specific emphasis on the role of heparin-binding protein (HBP) and resistin; recently identified markers of severity in sepsis.