Schizophrenia is a functional psychosis with a multifactorial etiopathogeny involving genetic, endocrine and immunological risk factors. The main pathogenic hypothesis involves dopamine dysregulation, with hyperfunction in the limbic system and hypofunction in the prefrontal cortex. Normal dopamine activity is critical for cognitive and emotional processing, but also for autonomic and immune regulation. Co-morbidity between schizophrenia and cardiovascular anomalies is complex. Genetic factors influence the development of brain, cardiac and vascular structures, as well as the activity of enzymes involved in dopamine synaptic turnover. Autoimmunity triggered by infections or related to systemic diseases affects both brain and heart in a direct manner through autoantibodies and/or indirectly through microvascular injury. In most cases, the co-morbidity between schizophrenia and cardiac diseases is secondary to metabolic dysfunctions induced by psychotropic medication or psychosis itself. Because of their diverse pharmacodynamic profiles, antipsychotics differ in their propensity to facilitate the development of the metabolic syndrome. The distress associated with acute psychotic symptoms or a sedentary lifestyle due to negative symptoms may have a negative impact on the energetic metabolism or cardiac function. Conclusions: An interdisciplinary approach is required between neurosciences and cardiology not only at the research level, but also in the clinical practice. Cardiac co-morbidity in subjects with schizophrenia may critically affect the survival rates of these patients. Moreover, the nature of the cardiac co-morbidity may guide the clinician in better understanding and differentiating functional psychoses from organic ones. The multifactorial approach can identify cardiovascular risk factors based on clinical, biological and neuroimaging markers.