The outcome of patients with sepsis arises from multiple factors affecting both the host and the invading microorganisms. Even within the setting of adequate antimicrobial use, patients still die of sepsis. Thus, strategies focusing on further therapy targets are an important area of interest for basic and clinical research. Although such adjunctive sepsis therapy has failed to achieve consistent better survival rates so far, the progress in understanding of the pathophysiology of sepsis seen in recent years is so profound, that the possibility that a new and effective treatment may arise should be warmly considered. Indeed, it may be considered that efficacious interventions, such as early and vigorous fluid replacement, strict blood glucose control, low-dose corticosteroid reposition, protective mechanical ventilation and activated-protein C are pathogenic-oriented targets of therapy. In this paper we aim to review some aspects of the pathogenesis of sepsis, focusing on possible targets for adjunctive therapy. Published clinical trials and experimental data supporting such trials are commented on.