Psoriasis is a common, chronic inflammatory skin disease associated with a large number of comorbidities. Though management of moderate-to-severe plaque psoriasis has greatly improved in recent years, patients with refractory disease or contraindications to available treatments still constitute therapeutic challenges. Oral roflumilast, a selective phosphodiesterase-4 (PDE-4) inhibitor, is approved for chronic obstructive pulmonary disease. Experimental studies have shown increased PDE-4 activity in psoriatic skin, and inhibition results in down-regulation of key inflammatory cytokines. Based on mode-of-action and available literature, we hypothesize that oral roflumilast is a future treatment for plaque psoriasis. Contrary to most existing psoriasis therapies, roflumilast has a favorable safety profile and holds the potential to improve not only skin manifestations but also commonly seen comorbidities. If efficacy and safety are confirmed in randomized settings, roflumilast can fill in a large unmet need and may represent a novel, relatively inexpensive, and convenient therapy positioned before biologics.