The remarkably high incidence of child maltreatment in the United States and worldwide is astounding. Estimates have revealed that nearly 3.6 million cases of child abuse and neglect are reported annually in the United States. According to the U.S. Department of Health and Human Services Children&rsquo;s Bureau (NCANDS), more than 700,000 of these were found to be severe in nature, with nearly 2,000 cases resulting in fatalities in 2007 alone. However, it is important to recognize that many experts in the field consider these figures to be a gross underestimate because childhood maltreatment is often not reported or difficult to confirm. A growing database indicates that early life stress, defined as verbal, physical or sexual abuse, or neglect, including, for example, separation from a primary caregiver, or living with a primary caregiver with severe mental illness, increases the risk of developing psychiatric disorders, including mood disorders, anxiety disorders, attention-deficit hyperactivity disorder (ADHD), substance abuse, and schizophrenia.<sup><a href="EditorPage.aspx?da=core&amp;id=%7bA932AC25-CB6C-41F0-887A-1F74731AC343%7d&amp;ed=FIELD17595849&amp;vs&amp;la=en&amp;fld=%7b0B37FA8E-B2A6-4AE9-8E4F-53651D5CB226%7d&amp;so=%2fsitecore%2fsystem%2fsettings%2fhtml+editor+profiles%2frich+text+healio&amp;di=0&amp;hdl=H17595923&amp;us=sitecore%5cadmin&amp;mo&amp;pe=0#x00485718-20091123-02-bibr1">1&ndash;4</a></sup> Moreover, the long-term effects of early-life trauma are not limited to increased vulnerability for syndromal psychiatric disorders but also appear to result in impaired cognitive abilities, increased obesity, and long-term effects on a number of biological systems that result in increased disease burden in adults. It is this subject that comprises the major subject matter of this article, an area previously, to the best of our knowledge, not summarized. Understanding the biological consequences of early-life stress is of paramount importance, not only in advocacy for protection of our youth but also as a pathophysiologic guide to develop novel treatments for this population. As will be described below, multiple biological mechanisms have been demonstrated to be dysregulated in adults who were victims of child abuse and neglect. These include effects on the endocrine, nervous, immune, and cardiovascular systems, all of which are known to be involved in the innate acute stress response. This article is an effort to consolidate the data available involving the long-term medical consequences of childhood trauma.