Tissue hypoxia can be defined as a state in which tissue oxygen demand is not met by tissue oxygen delivery (DO2). The presence and persistence of tissue hypoxia is related to the development of organ system failure and subsequent death. However, definite clinical indicators of tissue hypoxia are lacking. In experimental conditions, a mismatch between oxygen delivery and oxygen demand, resulting from either a progressive decrease of any of the components of oxygen delivery (hemoglobin level, arterial oxygen saturation and cardiac output) or an increase in oxygen demand, leads to increases in blood lactate levels. However, as lactate is a normal end product of metabolism, other processes not related to tissue hypoxia have also been linked to increases in blood lactate levels. In clinical conditions increased blood lactate levels and a failure to normalize blood lactate levels during treatment have been associated with increased morbidity and mortality. Even in hemodynamically stable patients with hyperlactatemia, a condition referred to as compensated shock or occult hypoperfusion, lactate levels are related to morbidity and mortality. In our retrospective pilot study, performed in the general ICU of the Erasmus MC (n= 931), we found 40% mortality in patients with blood lactate levels of 3 mmol/l or higher in the early hours of ICU admission. Blow at al. implemented a treatment protocol to increase oxygen delivery, guided by blood lactate levels, in hemodynamically stable trauma patients with occult hypoperfusion. Failure to correct hyperlactatemia after lactate-directed therapy correlated with increased mortality. Rossi et al. studied lactate-directed therapy in children undergoing congenital heart surgery. However, while showing a reduction in morbidity and mortality, they used a historical control group. Only one randomized controlled trial has been performed evaluating lactate-directed therapy. This study of Polonen et al. showed a decrease in morbidity and length of stay in post-cardiac surgery patients using lactate < 2mmol/l (and mixed venous oxygen saturation [SvO2] > 70%) as goals of therapy. Thus, a relevant body of clinical evidence does not yet support routine monitoring of blood lactate levels and lactate-directed therapy in all critically ill patients. As some investigators have even posed strong arguments that increased blood lactate levels are not related to the presence of tissue hypoxia in critically ill patients, some clinicians use increased blood lactate levels to guide therapy whereas others hardly measure lactate levels. The limited evidence of efficacy and the variable clinical use of blood lactate monitoring in different hospitals thus warrants a study on the clinical efficacy of blood lactate monitoring and blood lactate-directed therapy in the ICU.