Multiple observational studies have recently demonstrated associations between psoriasis and several comorbidities--especially metabolic syndrome and cardiovascular disease, and now osteoporosis. It has been hypothesized that elevated levels of tumor necrosis factor-alpha are a biological explanation for the observed associations. In this commentary, we discuss the complexity of associations between psoriasis and comorbidities, possible residual confounding, the limitations of observational studies in proving causality, absolute versus relative risk differences, and the clinical relevance and possible clinical impact of "upgrading" psoriasis to a systemic disease.