Life-threatening systemic insults or diseases often affect the brain. In critically ill patients, acute brain dysfunction manifests in several ways including reduced consciousness, coma, or delirium. The pathophysiology is complex, incompletely understood, and may relate to critical illness-related inflammatory changes, neurotransmitter imbalances, or failure of adequate energy substrate delivery [1], as well as to the applied treatments, pharmacological neurotoxicity, or the hostile ICU environment (Fig. 1) [2].