Depression is one of the most common mental health disorders and is ranked fourth in the cause of disability due to illness with constant growth tendency. Depression is a common disorder in cardiovascular patients with a prevalence of 20% to 45%, which is much more frequent than in the general population. Scientific studies have shown that the comorbid states between depression and cardiovascular disease have high prevalence and there is a common phenomenon of coexistence between these two entities. Mechanisms for the development of comorbidity are diverse and include genetic predisposition for mental and cardiovascular diseases, personality types, stress exposure, and increased incidence of unhealthy lifestyles. The pathophysiological association of depression and heart disease is related to autonomic nervous system dysfunction, hyperactivity of the hypothalamus-pituitary-adrenal gland (HHN os), endothelial dysfunction of the blood vessels, inflammatory conditions, platelet function, homocysteineemia, and numerous psychosocial factors. At the same time, treatment of both entities requires attentiveness of the physician when choosing pharmacological therapy due to complex interactions between psychotropic and cardiological drugs. In addition to pharmacological therapy, psychotherapy is also needed to prevent the occurrence of residual symptoms and to provide adequate quality of life for depressed cardiovascular patients.