Delirium is an acute neuropsychiatric syndrome reflecting serious cerebral dysfunction. The characteristic core symptoms of delirium include the inability to direct, focus, sustain, and shift attention; abnormalities of the sleep-wake cycle; impaired consciousness and awareness; disturbance of thought processes; and behavioral dyscontrol. Delirium is particularly prevalent in critically ill and post-operative patients in the intensive care unit, and may result from hypoxia or infection. It is most likely in the most severely ill, and length of stay is prolonged, and morbidity and mortality and higher with delirium. A variety of clinical instruments have been developed to facilitate the diagnosis of delirium. The Delirium Rating Scale, and its 1998 revision (DRS and DRS-R98) are for psychiatrists to use and are based on DSM criteria. The Pediatric Confusion Assessment Method, adapted for pediatric patients in the ICU (pCAM-ICU), is designed for non-psychiatrists and nurses in the intensive care unit. The Pediatric Anesthesia Emergence Delirium scale (PAED) is the basis for the Cornell Assessment of Pediatric Delirium (CAP-D), and both are for nurses and doctors in the pediatric ICU to use to identify delirium in their patients. Delirium is typically multifactorial and its pathogenesis reflects neurotransmitter changes associated with metabolic and inflammatory processes. Benzodiazepines and anticholinergic drugs, including opioids and antihistamines, are widely used in the pediatric ICU and may precipitate or exacerbate delirium. Benzodiazepines especially are best used sparingly, in the lowest dose possible, if at all. The treatment of delirium is predicated on detecting and addressing its underlying cause, which usually results in its rapid resolution. Environmental interventions may ameliorate the risk for delirium, and drugs which may precipitate or worsen delirium should be avoided. Antipsychotics can provide benefit in managing agitation, perceptual disturbances, sleep-wake cycle abnormalities, and behavioral dyscontrol. Atypical antipsychotics, including olanzapine, risperidone, and quetiapine, have largely replaced haloperidol in newer approaches to management because of lower risk for adverse side effects. The risk for delirium may be mitigated by vigilance, and awareness of its presentation, pathogenesis, and management. Its prevention will be of significant benefit in reducing morbidity, improving outcome, and providing comfort to these very ill and fragile children.