It has been long established that depression is an independent risk factor for cardiovascular disease (CVD) and that CVD is a risk factor for depression. Three lines of evidence have been proposed to date in an effort to explain the comorbidity of CVD and mood, as well as anxiety disorders:

1. (1) The epidemiological evidence for a causal role of depression in the evolution and progression of CVD;

2. (2) The biological evidence for the plausibility of an etiologic role of depression in CVD and

3. (3) Both depression and CVD are manifestations of a common underlying pathophysiological process. The goal of this presentation is to briefly review and synthesize the evidence for the above proposed explanations with a special focus on the roles of serotonin, platelets and the immune system. Sex and gender differences in both depression/anxiety and CVD and the relevance of these differences as they pertain to women will be emphasized.