Epidemiological studies have shown that, in psoriasis patients, associated disorders may occur more frequently than expected. Such comorbidities include psoriatic arthritis, psoriatic pustular diseases, Crohn disease, and signs of metabolic syndrome, which leads to atherosclerosis with coronary heart disease. Although the disorders represent separate entities, they appear to follow overlapping pathogenic pathways. Comorbidities often become clinically manifest years after onset of psoriasis and are frequently seen in severe disease. Persistent low-grade inflammation with secretion of proinflammatory cytokines (eg, tumor necrosis factor alpha) favors the development of insulin resistance and metabolic syndrome. In addition, biochemical and immunologic observations point toward an inflammatory immune mechanism that uses tools of the innate defense armamentarium.