Terror management theory outlines how humans seek self-esteem and worldview validation to manage death-related anxiety. Accumulating evidence reveals that close relationships serve a similar role. However, to date, there has been no synthesis of the literature that delineates when close relationships buffer mortality concerns, under what conditions, on which specific outcomes, and for whom. This systematic review presents over two decades of research to address these questions. Findings from 73 reviewed studies revealed that close relationships serve an important role in buffering death-related anxiety. A range of dispositional and situational moderating factors influence either the activation or inhibition of relational strivings to manage heightened death awareness, the most influential being attachment, gender, and relationship-contingent self-esteem. These findings were integrated into an overarching model that highlights some of the conditions under which mortality salience (MS) influences relational outcomes. We conclude by highlighting a range of theoretical and methodological concerns to be addressed by future research.