Critically ill intensive care unit (ICU) patients often require sedation to tolerate life-saving interventions such as mechanical ventilation. Pain, anxiety, and delirium all contribute to patient distress and agitation which can interfere with ICU medical care if not addressed and treated appropriately. Sedation practices to treat pain, anxiety, and delirium that deviate from established practice guidelines affect mechanical ventilation duration, ICU and hospital length of stay, functional impairment, and mortality. Historically patients were kept deeply sedated in the ICU. However, considerable research has demonstrated that minimizing sedation with the goal to achieve comfortable wakefulness is preferred in most ICU patients and is associated with improved clinical outcomes. This review will focus on changes in sedation practice in the ICU over the past three decades. With the implementation of validated sedation assessment scales, a multidisciplinary treatment model, and development of daily awakening protocols, no or minimal sedation can be achieved in the majority of ICU patients. Frequent, careful consideration of the environmental stimuli that contribute to patient discomfort and agitation and judicious use of sedative medications individualized to each patient are important in achieving this goal.