In last years opioids have been increasingly utilized to sedate patients during mechanical ventilation. First, in Hypnotic Based Sedation (HBS), they were added to hypnotics because of their analgesic properties. Successively, in Analgesic Based Sedation (ABS), both sedative and analgesic properties were utilized and opioids were given alone; hypnotics were added only if adequate sedation was not achieved at maximum dosage. Apart from their analgesic and sedative properties, opioid effects on respiratory function are of particular value in many mechanically-ventilated patients. Dose-dependent inhibition of respiratory drive may usefully prevent spontaneous breathing during controlled ventilation, particularly when permissive hypercapnia is applied, or decrease excessive respiratory rate during assisted or noninvasive ventilation. Even cough inhibition can be valuable in some conditions, for instance, during respiratory weaning and endotracheal tube removal in patients that should not cough because of a recent tracheal resection. On the other hand, excessive respiratory depression may cause hypoventilation and apnea during assisted or spontaneous ventilation and lengthens the weaning process. In order to take advantage from positive effects and to avoid negative ones, opioid dosage should be thoroughly titrated. On this basis remifentanil has become increasingly popular as the opioid agent most suitable for ABS because of its unique, favorable pharmacokinetics.