Borderline personality disorder (BPD) is a debilitating mental health condition that is highly associated with distress in close relationships and in romantic and nonromantic (e.g., familial) significant others. Interventions that efficiently improve BPD treatment outcomes are needed. Theory and research suggest that BPD may both promote and be maintained by close relationship distress. Incorporating significant others into BPD treatments may therefore present a novel and unique opportunity to maximize treatment outcomes. This work systematically reviews the empirical support for interventions that incorporate significant others in BPD treatment in addressing three potential treatment targets: (a) BPD pathology, (b) significant other distress, and (c) close relationship distress. Three distinct categories of intervention that involve significant others into BPD treatment are presented, and the interventions that fall within them are reviewed: (a) significant-other-assisted interventions, (b) education- and family-facilitated engagement interventions, and (c) disorder-specific interventions. Twelve articles outlining six treatments that vary in terms of potential treatment target, form of intervention, and level of empirical support are discussed. Interventions that target BPD in the context of close relationships, which are disorder-specific interventions, have amassed the most robust evidence base as an efficacious approach for all three targets at once. We conclude our review with a synthesis of the extant literature and offer future directions in terms of advancing theory to better understand and treat BPD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).