Although the relationship of mental health with cardiovascular dysfunction is not a recent finding, scientific data has appeared approximately at the middle of the last century. Firstly, depression was studied as a risk factor for premature death in cases of cardiovascular disease (CVD). Much later, the mechanism of psychosis and schizophrenia in the development of CVD were studied, as it was observed that most premature deaths in schizophrenia were related to cardiovascular disease. This interaction is supported both by epidemiological data and by the associated mechanisms. Inflammation, oxidative and biologic stress, and hormonal and neurotransmitter disorders in coagulation, tissue perfusion, vascular dysfunction and genetic factors get involved in these mental disorders. The combination of these pathophysiological mechanisms and the general risk factors for CVD (sex, age, smoking, systolic blood pressure, body weight, glucose levels) leads, to some extent, to increased rates of comorbidity and mortality. Patients with severe mental disorders are often not monitored and do not receive appropriate treatment for cardiovascular risk factors. In studies of patients with comorbid coronary heart disease and depression, there were signs of cardiovascular dysfunction, including increased heart rate, mainly in stress, QT prolongation and ventricular arrhythmia. At the same time, there is a dose-response relationship between the severity of depression and cardiovascular risk, with the presence of even mild symptoms of untreated depression involving some cardiovascular risk. In addition, improving the symptoms of depression through medication has been associated with increased survival. Moreover, the causes of increased mortality in patients with schizophrenia are similar to those of the general population with metabolic syndrome and diabetes mellitus, while failure to receive antipsychotic medication could lead to obesity, insulin resistance, dyslipidemia and hypertension. These data could be used as a source for future anti-inflammatory therapeutic approaches, but also for the appropriate selection of therapeutic agents, by taking a more holistic view of the patient’s comorbidity. The interdisciplinary collaboration and liaison – consultation psychiatry are important factors for the timely prevention, recognition and treatment of potent complications of the cardiovascular system in mentally ill patients. The aim of this review was to present the pathophysiological mechanisms of serious mental disorders, such as depression, bipolar disorder, and schizophrenia that may be related to the development of CVD.