There are a number of dimensions to the complex relationship between cardiovascular disease and affective disorders including: (i) patients with depression are at an increased risk of dying from sudden cardiovascular death compared with the general population; (ii) patients with depression over the course of a lifetime have a higher rate of symptomatic and fatal ischaemic heart disease compared with a control group without depression; and, (iii) patients after either a myocardial or a cerebrovascular infarction who are depressed have a higher mortality rate than their medically comparable nondepressed counterparts. The deleterious impact of depression on the prognosis of cardiac disease and the suggestion that treatment of depression may reduce cardiac mortality has led clinicians to seek safe and effective treatment for patients with comorbid depression and ischaemic disease. Though they are robustly effective, the tricyclic antidepressants are type 1A antiarrhythmic agents and presumably carry the same risk in patients with ischaemic disease as treatment with other type 1 antiarrhythmics such as moricizine. Short term studies of the safety of other antidepressant agents, specifically amfebutamone (bupropion) and the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) fluoxetine, paroxetine and sertraline, suggest that these medications have a benign cardiovascular profile in patients with depression and pre-existing cardiac disease. However, given the methodological limitations of study design and the relatively small number of patients included, it is premature to conclude that SSRIs are a 'safe' treatment in patients with heart disease. Thus, clinicians must still make treatment decisions on a case by case basis, considering the type and severity of depression and cardiovascular disease, as well as what is known about the cardiovascular effects and therapeutic profile of the different classes of antidepressant medications.