Pityriasis rubra pilaris is a rare inflammatory dermatosis characterized by orange-red confluent plaques, hyperkeratotic follicular papules, palmoplantar keratoderma, and, in some cases, erythroderma. The etiology of pityriasis rubra pilaris is unclear. This condition is often treated with oral retinoids and topical corticosteroids, and more recently, biological agents have become the mainstay of treatment. However, there is a paucity of high-quality evidence on the safety and effectiveness of these agents, and the disease often remains refractory to therapy. Herein, we present a case of pityriasis rubra pilaris with a favorable response to treatment with upadacitinib, a Janus kinase inhibitor, which has not been previously reported in the literature for the management of this condition.