Psoriasis is an inflammatory skin disease that is associated with many comorbidities. Several psoriasis treatments approved by the United States Food and Drug Administration have been shown to have beneficial effects on these comorbidities, while others might lead to an exacerbation of these conditions. In this article, we review studies of psoriasis treatments and their level of evidence for use in co-occurring diseases. An awareness of the multifaceted effects of certain psoriasis medications can enable physicians to provide more personalized treatment to their most complicated patients.