Biomedical researchers increasingly recognize that childhood events, specifically abuse and trauma, have profound and enduring effects on the neuroregulatory systems mediating medical illness as well as on behavior from childhood into adult life. Our understanding of the connection between trauma in childhood and the pathways to pathology in adulthood is still being formed as neuroscientists begin to describe the changes that take place on the molecular level as a result of events that occurred decades earlier. The turning point in modern understanding of the role of trauma in medical and psychiatric pathology is commonly credited to Freud, who studied patients of the French neurologist, Charcot, attributing their unusual behavior to histories of trauma rather than to underlying biomedical pathology. 2 Subsequently, the writings of Freud and Breuer as well as Janet represented a departure from the traditional view that mental illness and unexplained medical disease were the result of divine retribution or demonic possession, instead revealing that they were strongly associated with a history of childhood abuse. 3 The focus of this chapter will be an examination of the relationship between traumatic stress in childhood and the leading causes of morbidity, mortality, and disability in the United States: cardiovascular disease, chronic lung disease, chronic liver disease, depression and other forms of mental illness, obesity, smoking, and alcohol and drug abuse. To do this, we will draw on our experience with the Adverse Childhood Experiences (ACE) Study, a major American epidemiological study providing retrospective and prospective analysis in over 17,000 individuals of the effect of traumatic experiences during the first eighteen years of life on adolescent and adult medical and psychiatric disease, sexual behavior, healthcare costs, and life expectancy. 4