: Depressive disorders and cardiovascular disease are inter-connected by a whole range of pathophysiological mechanisms. Three biological mechanisms are fundamental: activation of the hypothalamus-hypohysis-adrenal axis with a subsequent increase in sympathetic-adrenal system activity, decrease in vagal tone with a decrease in heart rate variability, and alterations of thrombogenesis with increased platelet aggregability. Behavioural mechanisms and psycho-social factors are also integral to this common pathophysiology. Recently, research has focused mainly on studying various forms of stress, as well as changes and possibilities of influencing the autonomous vegetative system. Temporal aspects of the incidence and development of depressive episodes in relation to cardiovascular disease and subsequent cardiovascular morbidity and mortality are being studied, as well as general mortality risk factors. These findings are important for clinical practice. It is evident that in patients with untreated depressive disorder, the risk of developing cardiovascular disease is significantly higher than in patients suffering from a depressive disorder being treated with anti-depressants. From the data published so far, it may be surmised that depressive disorders in patients with cardiovascular disease may be reliably and safely treated with anti-depressants that act as inhibitors of serotonin re-uptake.