This article introduces the metabolic syndrome as a clinical phenotype with consequences for diagnosis and treatment that go beyond the different clinical specialties involved. A life-course approach is suggested as a means of understanding the complex interrelations between the metabolic syndrome, depression, and cardiovascular disease. Pathophysiologic mechanisms that these conditions share are discussed in detail. These considerations provide arguments for a more integrative approach to patients in general that surpass the current disease-centered services such as endocrinology, psychiatry, and cardiology.