Psoriasis is the most prevalent immune-mediated skin disease affecting 2-4% of the world's population. Severe psoriasis is a disabling disease affecting the physical and emotional well being of patients, and its effect on quality of life is similar to that seen with other major medical diseases such as diabetes, rheumatoid arthritis, and cancer. Psoriasis is a prototypical Th-1 and Th-17 inflammatory disease, which demonstrates a complex interplay between innate and adaptive immunity. Although the etiology of psoriasis in still not completely elucidated, on the basis of existing knowledge, it is obvious that psoriasis is a complex trait involving genetic, metabolic and immune mechanisms as well as environmental factors. Moreover, it is increasingly being recognized that psoriasis is not merely a skin disease but is probably associated with other co-morbidities such as psoriatic arthritis, Crohn's disease, the metabolic syndrome and CVD. Some of these co-morbidities often become clinically apparent years after the onset of psoriasis and are frequently found in patients with severe disease. Furthermore, recently, studies based on large cohorts of psoriasis patients showed that severe psoriasis was association with increased mortality and CVD was found to be the most common cause of death. The metabolic syndrome The metabolic syndrome is a combination of diabetes mellitus type II (or insulin resistance), hypertension, central obesity, and combined hyperlipidemia (elevated LDL; decreased HDL; elevated triglycerides). The prevalence of the metabolic syndrome in the USA is estimated to be up to 15% of the population. Obesity, which is a central feature in the metabolic syndrome, has been termed the modern "epidemic" of the western world. The metabolic syndrome components are associated with increased risk for CVD, which is still the leading cause of death in the western world. Interestingly, inflammation was also implicated in the pathophysiology of the metabolic syndrome. Th-1 and Th-17 cells and cytokines as well as other adipocyte-derived-cytokines adipokines and hormones were identified. Excess numbers of psoriatics are obese, interestingly, the average weight of patients in recent phase 3 studies was around 90Kg. Mechanistic links between psoriasis and its co-morbidities Low-grade inflammation possibly mediated by TNF is suspected to be the biological plausibility explaining the associations discovered in the epidemiological studies linking between psoriasis and its co-morbidities and especially the metabolic syndrome. Progress in understanding the immunology of these apparently diverse diseases has discovered common physiological pathways. Clearly many different tissues and organs have a common blood supply and can be exposed to increased levels of inflammatory cytokines, chemokines and other mediators through the systemic circulation. The "obesity of psoriasis" is thought to be a key link to the metabolic syndrome as well as to CVD. In the past, the only known adipose tissue functions were energy storing and free fatty acids production. However, a dramatic increase of research on the role of adipose tissue has led to the current view that adipose tissue is an active endocrine organ with many secretory products including adipokines and other cytokines. Moreover now it is also being recognized as a part of the innate immune system. Adipocytokines play important roles in the pathogenesis of insulin resistance and associated metabolic complications such as dyslipidemia, hypertension, and premature heart disease. TNF is a major mediator of disrupted insulin receptor signaling. Preventing co-morbidities In view of the chronic nature of the inflammation in psoriasis and the lingering process of metabolic syndrome and CVD development, the most important question is whether effective, long-term control of psoriasis could prevent, reverse, or attenuate these co-morbitides.