Pityriasis rubra pilaris (PRP) is a rare, chronic papulosquamous disorder of unknown etiology that often progresses to disabling palmoplantar keratoderma and erythroderma. There is currently no universally effective treatment for PRP, and some cases are resistant to multiple topical and systemic therapies. Systemic retinoids, methotrexate, several immunosuppressive agents, fumaric acid esters, stanozolol, and phototherapy have all been used with varying degrees of success. Recently, a few reports have appeared in the literature concerning the use of biologics in combination therapies and/or in refractory PRP cases. We report a case of type I adult-onset PRP successfully treated with infliximab monotherapy as initial systemic therapy, and provide a comprehensive literature review on biologic therapy for PRP. The complete and persistent response to infliximab in our patient and in the previously reported cases confirms a role for anti-tumor necrosis factor-alfa therapy as an effective option in the treatment of PRP. Further studies are warranted to evaluate possible differences in efficacy among the different biologics.