Borderline Personality Disorder (BPD) has been often described recently as a condition characterized by emotional dysregulation. Several other conditions share this attribute; namely, Bipolar Disorder (BD), Attention-Deficit/Hyperactivity Disorder (ADHD), Intermittent Explosive Disorder (IED), and Major Depressive Disorder (MDD). The dysregulation is not always in the same direction: BPD, BD, ADHD, and IED, for example, show over-reactivity or "hyperactivity" of emotional responses, whereas patients with MDD show emotional sluggishness and underactivity. At the clinical/descriptive level the "over-reactive" conditions appear separate and distinct. BPD constitutes a large domain within the psychopathological arena, appearing to contain within it a variety of etiologically diverse subtypes. Among the latter is a type of BPD linked closely with Bipolar Disorder; family studies of either condition show an overrepresentation of both: BPD patients with bipolar relatives; Bipolar patients with BPD relatives. A significant percentage of children with ADHD go on to develop either BPD or BD as they approach adulthood. If one shifts the spotlight to neurophysiology, as captured by MRI studies, however, it emerges that an important subtype of BPD, and also BD, ADHD, and IED-share common features of abnormalities and peculiarities in the limbic system and in the cortex, especially the prefrontal cortex. Deeper subcortical regions such as the periaqueductal gray may also be implicated in strong emotional reactions. The diversity of clinical "over-reactive" conditions appear to harken back to a kind of unity at the brain-change level. There are therapeutic implications here, such as the advisability of mood stabilizers in many cases of BPD, not just for Bipolar Disorder.