Child abuse and neglect confer substantially increased risks of developing post-traumatic stress disorder (PTSD) for the victims and possibly even their offspring. Furthermore, they are associated with more severe and treatment-resistant PTSD and common comorbid conditions, such as major depressive disorder. This chapter begins by discussing the epidemiology of child abuse, neglect, and maltreatment-associated PTSD to provide a sense of the nature and scope of these major public health problems, then describes the major ways in which child abuse and neglect may contribute to increased liability to PTSD: maltreatment, victim, and environmental factors; neurobiological changes, including neuroendocrine, neurotransmitter system, structural and functional neuroimaging, inflammatory, and epigenetic changes; interactions with risk gene alleles; and cognitive, psychological, and behavioral changes. A discussion of the implications of this knowledge for future research and the development of new treatments for child maltreatment–associated PTSD follows.