Treatment recommendations for pityriasis rubra pilaris (PRP) are based solely on case reports and small case series, as to-date no randomized controlled trials are available. We present here a case series of 3 patients and a literature review of 28 studies treating a total of 116 patients, with the aim of providing data regarding efficacy and safety of methotrexate in the treatment of PRP. Methotrexate was effective in our patients; the review showed an overall response rate of 65.5% with complete clearing in 23.3% and excellent improvement in 17.2%, respectively. After excluding studies with other concurrent systemic therapies or low reliability, the overall response rate increased to 90.9%, with complete clearing in 40.9% and excellent improvement in 31.8%, respectively. Sixteen adverse reactions, of which 11 were mild, were observed in 15 patients (12.9%). In conclusion, the available literature supports good response rates and safety of methotrexate in PRP.