In recent years the problem of infection has become increasingly significant, especially in intensive care hospital wards such as Intensive Care Units (ICU), emergency medicine, surgery and critically ill patient care departments. Sepsis is a complex, multifactorial syndrome that can develop into conditions of different severity, described as severe sepsis or septic shock. In these conditions the triggering event may coincide with the functional impairment of one or more vital organs or systems, thus leading to poorer prognosis in patients with overt signs of sepsis or systemic inflammation syndromes. The available data are quite alarming, as most prevention and treatment is performed empirically and requires considerable human and technological resources. Clinical signs are often misleading and, in some circumstances, it may be difficult or even impossible to identify the source of the infection which might otherwise be removed relatively simply, using proper antimicrobial treatment or a less invasive surgical removal of the area from which the infection originates based on needle-guided radiology. In addition, the complex pathophysiological mechanisms involved can be an obstacle to gaining a full understanding of the various biohumoral interactions or mediators action mechanisms. It may not be easy to enroll patients belonging to homogeneous groups in terms of age, underlining disease, immune profile or genetic predisposition, although the use of specific severity indexes has proved helpful also to establish the prognosis. Although the interpretation of generalised inflammation as a warning sign also in the absence of clear signs of infection or a state of overt inflammation has to rely largely on simple intuition, it has helped to drive experimental and clinical research work towards the investigation of interaction between different factors such as infection and sepsis, or inflammation and coagulation. An additional useful tool is the possibility of modulating the endothelial response which may support the process of disseminated thrombosis typical of sepsis evolution. In this context the improvement of standards of care can shed light on the efficacy of different treatments.