As summarized in the first article in this continuing medical education series, the currently available epidemiologic data suggest that psoriasis may be a risk factor for cardiometabolic disease. Emerging data also suggest associations between psoriasis and other comorbidities beyond psoriatic arthritis, including chronic kidney disease, inflammatory bowel disease, hepatic disease, certain malignancies, infections, and mood disorders. Recognizing the comorbid disease burden of psoriasis is essential for ensuring comprehensive care of patients with psoriasis. The clinical implications of the comorbid diseases that are associated with psoriasis and recommendations for clinical management are reviewed in this article.