Acute hyperglycemia frequently present in stress conditions, has long been generally accepted as normal, and not thought to be a cause for concern since a moderate hyperglycemia in critically ill adult patients has been thought to be beneficial during the “fight or flight” response to ensure a supply of glucose as a source of energy to organs that do not require insulin for glucose uptake (i.e., the brain and the immune system). However, an increasing body of evidence associates the upon-admission degree and duration of hyperglycemia during critical illness with an adverse outcome. Hyperglycemia should be regarded as a part of the systemic and complex metabolic derangements observed in critical illness in response to stress and inflammation, which can lead, independent of initial disease, to multiorgan dysfunction and death. A tight glycemic control should be constantly pursued and achieved by insulin infusion bearing in mind that the therapeutic target is fighting the systemic inflammatory response and not merely the glucose plasma levels.