Sedation has become an important part of critical care practice in minimizing patient discomfort and agitation during mechanical ventilation. Pain, anxiety, and delirium form a triad of factors that can lead to agitation. Achieving and maintaining an optimal level of comfort and safety in the intensive care unit plays an essential part in caring for critically ill patients. Sedatives, opioids, and neuromuscular blocking agents are commonly used in the intensive care unit. The goal of therapy should be directed toward a specific indication, not simply to provide restraint. Standard rating scales and unit-based guidelines facilitate the proper use of sedation and neuromuscular blocking agents. The goal of sedation is a calm, comfortable patient who can easily be aroused and who can tolerate mechanical ventilation and procedures required for their care.