Posttraumatic stress symptoms have been reported in response to various serious medical illnesses in adults and children. Not surprisingly, posttraumatic stress is probably more common in response to acute, life-threatening, events that are related to the illness. Emerging data suggest that children often experience life-saving medical procedures as traumatic, which puts caretakers and medical personnel in the role of perpetrators for the children. Trauma symptoms are also reported as common and severe in caregivers. Both of these issues have been previously poorly understood and should be addressed in assessment and treatment. As with other traumatic events, developmental considerations, the nature and severity of the event itself, social supports, and premorbid exposure to negative life events are also important issues to consider in developing appropriate interventions. The importance of developing prevention and treatment for PTSD in medically ill children and adults includes increased morbidity and mortality (e.g., nonadherence to medications) and psychiatric sequelae and decreased quality of life. Obstacles to systematic study of a psychiatric intervention for this group include difficulties assessing multidrug regimens and cognitive treatment effects in this group. The relative stability of social supports and the potential use of preventive measures make this an attractive population for intervention. Clinicians and researchers are encouraged to work together to develop and use uniform screening and assessment methods that will help to identify cases and facilitate the multicenter trials that are vital to increasing knowledge in this patient population.