Psoriasis is a chronic inflammatory, immune-mediated skin disease, which affects 2%-3% of the population worldwide. Chronic plaque psoriasis is frequently associated with metabolic diseases including diabetes, obesity, dyslipidemia, metabolic syndrome and nonalcoholic fatty liver disease. Although the causal relationship between metabolic comorbidities and psoriasis has not yet been completely proven, it appears that shared genetic links, common environmental factors and/or common inflammatory pathways may underlie the development of psoriasis and comorbidities. The presence of comorbidities has important implications in the global approach to patients with psoriasis. Traditional systemic anti-psoriatic agents could negatively affect cardio-metabolic comorbidities, and may have important interactions with drugs commonly used by psoriatic patients. In contrast, the recent findings that the risk of myocardial infarction is reduced in patients with rheumatoid arthritis who respond to anti-TNF-α therapy compared to non-responders, supports the hypothesis that the anti-inflammatory effect of TNF-α blockers might reduce the cardiovascular risk potentially also in psoriasis patients. Finally, patients with moderate to severe psoriasis should be treated promptly and effectively, and should be encouraged to drastically correct their modifiable cardiovascular risk factors, in particular obesity and smoking habit.