Psoriasis is a chronic inflammatory, immune-mediated skin disease, which may cause significant deterioration in the quality of life. Recent evidence indicates that psoriasis and psoriatic arthritis are frequently associated with cardiometabolic diseases including myocardial infarction, stroke, diabetes, obesity, dyslipidemia and non-alcoholic fatty liver disease. Although the causal relationship between cardiometabolic comorbidities and psoriasis has not yet been completely proven, it appears that obesity is a relevant risk factor for the development of psoriasis and metabolic syndrome. In addition, moderate to severe psoriasis itself is a risk factor for cardiovascular disease and the metabolic syndrome. Some common genetic traits as well as inflammatory mechanisms may underlie the development of psoriasis and cardiometabolic comorbidities. The presence of comorbidities has important implications in the global approach to patients with psoriasis. Traditional systemic anti-psoriatic agents could negatively affect cardiometabolic comorbidities, and may have important interactions with drugs commonly used by psoriasis patients. In contrast, the recent findings that the risk of myocardial infarction is markedly reduced in rheumatoid arthritis patients who respond to anti-TNF-alpha therapy compared with non-responders supports the hypothesis that the anti-inflammatory effect of TNF-alpha blockers might potentially reduce the cardiovascular risk also in psoriasis patients. Finally, patients with moderate to severe psoriasis should be treated promptly and effectively, should also be encouraged to drastically correct their modifiable cardiovascular risk factors, in particular obesity and smoking habit.