Abstract: Objective: A bidirectional relationship between depression and cardiovascular disease (CVD) including biological mechanisms has been proposed; however, the potential role of clinical and sociodemographic moderators in this relationship remains unclear. We aim to systematically review the moderating influence of the clinical and sociodemographic variables on the observed interrelationship between depressive disorders and CVD.Method: We systematically reviewed MEDLINE, The Cochrane Library and PsycINFO databases. After the exclusion of articles, 101 remained for this review.Results: Several studies suggest that clinical characteristics of depression, such as severity of depression, number of episodes and duration of depression, may moderate the relationship between depression and cardiovascular disease. Consistently, various studies support a role for marital status, education and income as moderators of this relationship. Several of these studies vary in methodology, hence yielding some inconsistent results. Longitudinal and controlled studies are required to investigate the effect sizes of these moderating factors on the depression–CVD relationship.Conclusions: Clinical characteristics of depression and sociodemographic factors appear to be moderators in the bidirectional relationship between depression and cardiovascular disease. Further research should consider these factors in conjunction with subtypes of depression and biological markers in a comprehensive model of this interrelationship. Our findings may assist with clinical decision-making processes.