The care of the critically ill child often includes medications used for the relief of pain and anxiety. Children have key differences in pharmacokinetics and pharmacodynamics compared with adults that should always be considered to achieve safe medication use in this population. Pain must be addressed, and sedative use should be minimized when possible. Our understanding of sedation safety is evolving, and studies have shown that minimizing exposure to multiple medications can reduce the burden of delirium and iatrogenic withdrawal.