The aim of sedation and analgesia is to prevent secondary brain insult. The goals of sedation are the prevention and treatment of intracranial hypertension and systemic disorders. In such situation, the use of sedative and analgesic therapy should respect the rate of cerebral blood flow/cerebral oxygen consumption coupling while preserving cerebral perfusion pressure and decreasing the intracranial pressure. This treatment should have an analgesic and myorelaxing action with short and predictable time of action. The optimal agent with all these characteristics does not exist, but the combination of several pharmacological compounds may reach this goal. Benzodiazepines are the most frequently agents used. In most of cases they are associated with analgesics like opioids or ketamine. Opioids are the basis of analgesia because they do not produce brain haemodynamic alterations if arterial pressure is maintained. Ketamine, which use in this indication is matter of debate, has the advantage to maintain haemodynamics. Ketamine has no side effects on brain haemodynamics when used in combination with propofol or midazolam. Because of their side effects on haemodynamics and immune response, barbituric are no longer used as long term sedative agents. However, they are still recommended in cases of refractory intracranial hypertension. Propofol remains the optimal sedative agent because of its short duration action although its use is restricted because it is an expensive drug. Its use is recommended for short time sedation with or without opioids. The use of neuromuscular blockers should be focused on the patients with an intracranial hypertension refractory to standard treatment. The presence of brain damage in patients makes difficult to assess the level of sedation. One should avoid over sedation, which increases morbidity by prolongation of the duration of mechanical ventilation.