Physical and mental illnesses interact mutually and share common risk factors with not only additive but also synergistic effects. Comorbidity is a complex event for its numerous clinical and socio-environmental implications. Up to 25% of patients with chronic illness also suffer from comorbid mental disorders, even higher rates of comorbidity are seen for specific conditions (e.g. cancer, neurological disorders). Doctors tend to concentrate on symptoms and organs, underestimating the importance of mental health problems, especially when they accompany a serious physical illness. This is largely in the belief that the mental health issues, as simple corollaries of the major disease, are destined to disappear with the improvement of the physical disease. On the other hand, psychiatrists, physicians for psychosomatic medicine and psychotherapy, and psychologists may be similarly reluctant to deal with medical comorbidities in their patients. Such poor attention paid to the interplay between physical and mental disorders impacts negatively in terms of health and social costs, because of intensive, excessive or inappropriate use of resources as well as indirect costs (decrease in productivity, disability, reduced quality of life). These costs would be avoidable with the implementation of integrate and innovative interventions addressing effectively bio-psycho-social complexity. Such is indeed one of the absolute future priorities in health management worldwide.