One of every 3 patients admitted in an intensive care unit undergoes mechanical ventilation. Sedation and analgesia are required to facilitate patient tolerance to such an aggressive procedure, diminishing stress response, relieving pain and anxiety, ensuring patient comfort, and facilitating nursing care. However, misuse of sedatives and analgesics may impact negatively on critically ill patients. The recognition of the potential for enduring effects derived from sedative and analgesic misuse, the availability of new agents, and the growing emphasis on cost containment have led to important changes in the way that sedation and analgesia practices are implemented. The aim of the present review is to discuss the agents, indications, complications, and most important strategies to optimize the sedation and analgesic practices in the intensive care unit.