Sedative and analgesic agents remain some of the most commonly administered pharmacological treatments in pediatric intensive care units (PICUs) around the world. Their administration is necessary to facilitate the invasive, painful, or uncomfortable interventions that critically ill children require. Whilst, over the last couple of decades, there have been significant improvements in many of the elements of pediatric critical care that we frequently deliver, the provision of sedation and analgesia has changed relatively little. However, the evolution of pediatric critical care medicine has seen a remarkable improvement in critical care survivorship and our focus must shift to facilitating survival at minimum cost, rather than survival at any cost. It is well established that sedative and analgesic agents are associated with toxicity, tolerance, iatrogenic withdrawal syndrome, and delirium; and there may also be long-term neurologic, psychological, and psychiatric effects in critical care survivors that we can modify. Our goal must be to administer the smallest number of sedative and analgesic agents possible, in the lowest doses possible, for the shortest amount of time feasible, whilst controlling the pain and agitation of our patients. In order to achieve optimal outcomes, we must integrate our sedation and analgesia strategies with evidence-based evolving bundles of care, such as the ICU Liberation ABCDEF bundle, aimed at reducing iatrogenic harm.