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This chapter presents a general approach to pediatric sedation, focusing on the unique variables children bring to this clinical setting. It lays emphasis on the specific settings for pediatric sedation and the interplay between setting and sedation plan, clinical preparation, and the potential limitations or complications that must be understood. Knowledge of specific developmental issues (anatomical, physiological, and behavioral) is a prerequisite before provision of sedative drugs. The chapter focuses on the adverse airway events, and presents a brief review of the pediatric airway. The pharmacodynamics and pharmacokinetics of typical sedatives in children has slowly emerged for many agents over the years. While propofol remains an excellent sedative drug for the pediatric intensive care unit (ICU), its use now requires careful clinical monitoring and caution. Finally, the chapter presents the general comments regarding the most frequently used sedatives, with particular emphasis on the unique characteristics of each.