Psoriasis has been associated with a number of behavioral and systemic comorbidities, including psoriatic arthritis, anxiety, depression, obesity, hypertension, diabetes mellitus, hyperlipidemia, metabolic syndrome, smoking, cardiovascular disease, alcoholism, Crohn's disease, lymphoma, and multiple sclerosis. Many of these conditions have a similar immunologic pathogeneses. Canadian and international studies have not only confirmed the presence of these comorbidities but also have demonstrated that patients with psoriasis have a significantly reduced life span. Given that patients with psoriasis are often unaware of their comorbidities, they should be screened for these conditions and treated if required by their dermatologist and/or primary care physician. It is important to keep in mind that the comorbidities and drugs used to treat them have an impact on the choice of antipsoriatic treatment. In addition, comorbidities often preclude the use of traditional systemic agents. Recent studies have demonstrated that patients with preexisting comorbidities can be safely and effectively treated with biologic therapy. Furthermore, literature is evolving to suggest that better control of psoriasis might decrease cardiovascular mortality and prolong life.