The alleviation of discomfort and distress is an essential component of the management of critically ill surgical patients. Pain and anxiety have multifocal etiologies that may be related to an underlying disease or surgical procedure, ongoing medical therapy, invasive monitors, an unfamiliar, complex and chaotic environment, as well as fear. Pharmacologic and non-pharmacologic therapies have complex risk benefit profiles. A fundamental understanding of analgesia, sedation, and delirium is essential for optimizing important outcomes in critically ill pediatric surgical patients. There has been a recent emphasis on goal directed, evidence based, and patient-centered management of the physical and psychological needs of these children. The purpose of this article is to review and summarize recent advances and describe current practice of these important subjects in the pediatric surgical intensive care environment.