Sepsis and systemic inflammatory response syndrome-induced severe disruption of microcirculation and consecutive tissue hypoxia is considered a key factor in the development of organ dysfunction and multiple organ failure. The conventionally measured global variables such as lactate or macrohemodynamic parameters using a pulmonary artery catheter do not adequately mirror microcirculatory disturbances. Evaluation of the severity of microcirculatory distress and the effectiveness of resuscitation strategies requires new clinical technologies aimed at the microcirculation. It is anticipated that novel techniques such as optical spectroscopy and intelligent biosensors will play a major role in the development of new monitoring systems. In general, the current monitoring of organ dysfunction is characterized by a trend from invasive to noninvasive and "safe" techniques, which provide bedside or even on-line monitoring and allow a more precise and earlier detection of organ dysfunction. Techniques for the assessment of regional perfusion and microcirculatory bioenergetics to direct therapeutic procedures are expected to refine and optimize clinical treatment of critically ill patients in the future. This article addresses the question of which variables should be monitored, what is feasible, and what is valid for therapeutic consequences. Recent developments in monitoring of macro- and microcirculation and organ-specific dysfunction, e.g., lung, kidney, are described with respect to their advantages and limitations, and future directions are outlined.