There is lack of information and evidence-based studies on the treatment of pediatric pustular psoriasis. Previous reports have emphasized the limitations of the existing data and encouraged the exploration of therapy optimization through more structured research. The objective of the current study was to perform a systematic review of systemic interventions for pediatric pustular psoriasis with an emphasis on clinical response and treatment outcomes. A systematic literature search was conducted using the PubMed and Embase databases from 1982 to 2012. Of 632 references identified, 14 met our inclusion criteria and were included in the analysis. A cohort of eight patients from the Hospital for Sick Children, Toronto, Canada, was also included. Information was limited to systemic treatments in children. Only English- and Spanish-language articles were included. Information was gathered from 24 patients, 22 of whom (92%) presented with generalized pustular psoriasis and 2 (8%) with acral distribution. The mean age at presentation was 6.3 ± 4.9 years. More than one intervention was required in 12 (50%) cases. The most common therapies used for generalized pustular psoriasis were acitretin, cyclosporine, and methotrexate. We identified that there is lack of information regarding long-term response to systemic drugs because the data were focused on treatment initiation. Treatment of pustular psoriasis in pediatrics is challenging. Although acitretin, methotrexate, and cyclosporine seem to control generalized pustular psoriasis within 3 months of therapy initiation, information on long-term follow-up is lacking. Furthermore, physicians may encounter difficulties after discontinuing or tapering medications.