To review the literature related to recent temperamental and biological findings on borderline personality disorder (BPD) and major depression, the close link between the two disorders, and the latest therapeutical findings on BPD, focusing on the conditions of co-morbidity between depression and BPD. The National Institutes of Health's PubMed database was used to identify indexed studies on BPD, depression and the co-morbidity between the two. Only studies published between 2000 and 2011 were assessed. Similar temperamental features have been demonstrated in BPD and depression. The strong link between the two disorders seems to be widely recognized by scientific community. Psychotherapy and new antipsychotics are the topics of current major interest of research. The therapeutic targets in the case of co-morbidity are BPD features associated with depressive symptoms, thus influencing prognosis. A global assessment is, in fact, fundamental for a successful therapy for the treatment of the several aspects of a complex psychopathological phenomenon.