Borderline personality disorder (BPD) has been recognized as heterogeneous, etiologically, stemming from many combinations of genetic and environmental factors BPD never occurs alone: it is always accompanied by traits of other personality disorders and by various symptom-conditions, especially mood disorders. The controversy about linkage between BPD and bipolar disorder could not be resolved when the debate relied only on clinical description. Some twin-studies suggested modest overlap between BPD and bipolar disorder. Current neuroimaging research points to similarities in brain changes among several conditions characterized by emotional over-reactivity to stress: bipolar disorder, certain cases of BPD and attention-deficit hyperactivity (ADHD). These include alterations in the limbic system (e.g., amygdala and hippocampus) and neocortex (especially the prefrontal cortex). An important subset of BPD exists in which brain changes are essentially identical with those of bipolar disorder. Relevant brain-change findings and treatment implications are summarized in this article.