Patients with acute or chronic ischemic heart disease have a high incidence of depression, and a variable proportion of patients (ranging from 14% to 47%) suffer from major or subclinical depression. In addition, chronic depression has been shown to be associated with the development or progression of coronary atherosclerosis. Besides a poor quality of life, depressive symptoms in patients with ischemic heart disease result in a poor prognosis, as cardiovascular event rates are 2-2.5 times higher than in their counterparts without depressive symptoms. A variety of pathogenetic mechanisms may play a role, including pathophysiological (dysfunction of the autonomic nervous system or hypothalamic-pituitary-adrenal axis, platelet hyperaggregability, inflammation, endothelial dysfunction and genetic predisposition) and behavioral mechanisms (inadequate therapy adherence, obesity, smoking, sedentary lifestyle). However, in patients with ischemic heart disease, depression often goes undiagnosed or untreated. Several screening procedures including questionnaires for patients with heart disease, along with the help of a psychiatrist, may facilitate not only the diagnosis of depressive symptoms but also the pharmacological and/or physiotherapeutic management. The use of tricyclic antidepressant agents should be avoided in patients with heart disease, whereas selective serotonin reuptake inhibitors have been shown to be safe in this patient population. However, no evidence is available to support that use of these drugs is associated with a reduced risk of cardiovascular events at follow-up. Psychotherapy proved to be effective in reducing depressive symptoms but ineffective in improving prognosis. In this review, epidemiology and pathophysiology of depression in patients with ischemic heart disease are described, with a focus on stratification of depressive symptoms and potential therapeutic strategies.