Safe sedation of pediatric patients requires a thorough understanding of the physiological differences between infants, children, adolescents, and adults. Especially in small infants, there is a much less margin for any errors in diagnosis and treatment of respiratory or cardiovascular depression during sedation procedures. This chapter will review the developmental aspects of respiratory, cardiovascular, central nervous system (CNS), renal, hepatic, hematological, and temperature homeostatic systems, highlighting the differences between children and adults and emphasizing their relevance to sedation procedures in children.