Psoriasis is a common chronic inflammatory, immune-mediated skin disease that is frequently associated with comorbidities including psoriatic arthropathy, chronic inflammatory bowel diseases, and cardio-metabolic disorders. In particular, nonalcoholic fatty liver disease affects about half of patients, Crohn's disease 0.5% and celiac disease 0.2–4.3% of patients with psoriasis. Some shared genetic traits as well as common inflammatory pathways may underlie these associations. The presence of comorbidities has important implications in the global approach to patients. In particular, traditional systemic antipsoriatic agents could negatively affect cardio-metabolic comorbidities as well as nonalcoholic fatty liver disease and may have important interactions with drugs commonly used by psoriasis patients. Moreover, patients with psoriasis should be encouraged to drastically correct their modifiable cardiovascular and liver risk factors, in particular obesity, alcohol consumption, and smoking habit, because this could positively affect both psoriasis and their life expectance.