The health impact of heart disease and depression is immense. Depression is the estimated leading cause of disability worldwide [1] and heart disease is the leading cause of death and disability in Canada [2]. Over the past two decades, research has demonstrated that depression and heart disease are common companions and, more importantly, each can lead to the other. Studies have identified the prevalence of major depression in patients with cardiovascular disease as between 16 and 23% [3–6], while 65% of patients manifest symptoms of major or minor depression following myocardial infarction (MI) [7]. It has been reported that depression following episodes of acute coronary syndrome (ACS) is associated with major cardiac events [8], a 2.5-fold increase in the risk of a heart attack [9] and a threeto fourfold increase in cardiac mortality [4,10–14]. Furthermore, depression predicts a slow recovery and a poor quality of life [15,16]. These statistics led the investigators of the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) to comment that “depression that recurs or persists in ACS should be identified and treated because it is a serious illness that is both painful to patients and impedes their medical care” [17]. Behavioral and physiological mechanisms have been proposed for the association between depression and coronary artery disease (CAD) [18]. Aside from the fact that depressed individuals are more likely to engage in risk-related behaviors such as smoking or lack of exercise, studies have identified a number of neurohormonal sequelae [14,19–22] ensuing from acute stress and the resulting effects on cardiovascular function in depressed individuals [18]. These include hyperactive hypothalamic–pituitary–adrenal responses to stress, higher levels of norepinephrine and its metabolites in blood and urine, and reduced heart variability (beat-to-beat fluctuations in heart rate). Reduced heart variability has been validated as a measure of autonomic regulation of the heart and is associated with poor cardiovascular outcome [23,24]. It has been proposed that the loss of cardiac parasympathetic control leaves the heart vulnerable to unopposed stimulation by the sympathetic nervous system under stressful conditions, which predisposes depressed individuals to lethal arrhythmias [14]. Finally, there is also evidence that the association between depression and CAD is mediated, at least in part, by changes in platelet function [25]. Women are at greater risk for major depression as compared with men [26,27]. It has been found that women experience more depressive symptoms following MI compared with men [14,19–22], and that older women are found to suffer more, demonstrating more depressive symptoms including slowed speech and movement, disinterest in eating and exhausting fatigue [28]. Furthermore, depression has been proposed as being strongly associated with women’s overall poorer recovery from cardiac events [5,8,21,29–31]. It has been reported that women with CAD are older, have a higher burden of comorbid illnesses [28], are more often widowed, more likely to live alone, have more depressive symptoms and have poorer psychosocial adjustment following a CAD event [32–34]. In addition, there is growing evidence suggesting that CAD presents differently in women and men [35], which in turn contributes to gender differences in the delivery of care [28].