Sepsis syndrome, a systemic response to infection, can beget devastating outcomes even in previously normal individuals. Recent research in septic patients has led to the discovery that early goal-directed resuscitation guided by continuous monitoring of mixed venous hemoglobin saturation, along with moderate doses of corticosteroids, can reduce mortality. An improved understanding of the complex interaction between the inflammatory and coagulant systems in sepsis pathophysiology has resulted in novel treatments, such as recombinant human activated protein C, which improves survival in patients with severe sepsis and a high risk of death. However, despite an increased understanding of the complex pathophysiology of this syndrome and the discovery of new, effective treatments, severe sepsis still results in significant morbidity and mortality. Consequently, investigations continue into additional therapeutic agents directed against novel targets. Following a review of recent advances in sepsis treatment, we briefly discuss a few of the new, promising therapeutic strategies currently being investigated.