The consideration of chronic depression and personality disorders involves addressing an interaction between Axis I and Axis II disorders. The interaction between an Axis I mood disorder and an Axis II personality disorder has been looked at from many different points of view, but in general studies have explored the interaction or overlap between major depressive episodes and the specific personality disorder, borderline personality disorder (BPD). In this chapter, we will briefly explore and try to understand the relationship of the Axis I condition that here is referred to as “chronic depression” to the general group of personality disorders and not just to BPD, even though most of the data have been generated from studies involving BPD. In fact, in the early 1980s, soon after the publication of DSM-III (Diagnostic and Statistical Manual of Mental Disorders, 3rd ed.), there was a flurry of papers declaring that BPD was actually a variant of an affective disorder (Akiskal, 1981; Akiskal, Chen, Davis, Puzantian, Kashgarian, & Bolinger, 1985a; Akiskal, Yerevanian, Davis, King, & Lemmi, 1985b; Carroll et al., 1981; Liebowitz & Klein, 1981). We make note that this chapter does not review the overlap of depression and personality, a topic that has been dealt with, though not resolved, in many papers in the literature (Akiskal, Hirschfeld, & Yerevanian, 1983; Fava, Alpert, Borus, Nierenberg, Pava, & Rosenbaum, 1996; Gold & Silk, 1993; Gunderson & Elliott, 1985; Gunderson & Phillips, 1991; Hirschfeld, Klerman, Clayton, Keller, McDonald-Scott, & Larkin, 1983; Klein, Kupfer, & Shea, 1993; Pilkonis & Frank, 1988; Ramlint & Ekselius, 2003; Shea et al., 1990; Widiger, 1993). Rather, this chapter tries to understand the nature of what chronic depression is or may be in the context of patients with personality disorders.