One of the greatest challenges that doctors face is treating patients with multimorbid conditions (often including psychiatric factors), defined as the complex medically ill. It is extremely important to understand how different diseases and disorders are interrelated, and how best to treat a patient who presents with multiple problems from multiple and overlapping sources. A good example of this is the metabolic syndrome. It is used as an example of a generic pathophysiological model for the interrelation of diabetic and cardiovascular disease, and depression. The efficacy of disease-focused versus integrated treatment is examined. The goal of this issue is to help physicians transition from fragmented care to integrated care on a clinical level. It presents effective and practical models for integrated care, while also examining the epidemiology of fragmented care and its consequences for quality of life, morbidity, mortality, and costs. The complexity of multiprofessional communication, and its measurement and decision support are addressed.