The interplay of pain, discomfort, and fear can cause agitation in critically ill children. Therefore, sedation and analgesia are essential components in the intensive care unit setting and are best managed with a multidisciplinary team approach. No one standard approach exists to assess and manage pain and anxiety. Many tools are available for the assessment of pain and sedation, but each tool has its advantages and disadvantages. Clinicians should consider adopting a validated tool for routine continuous assessment. Multiple pharmacological therapies are available to manage pain, anxiety, fear, and agitation. Dosing of these agents can be influenced by age-related pharmacokinetic and pharmacodynamic changes. Agents should be selected on the basis of the child's disease state, desired level of sedation, and cardiac and respiratory status.