Generalized pustular psoriasis (GPP) is a rare, severe form of pustular psoriasis. It is characterized by recurrent flares of widespread sterile pustules with erythematous, painful skin. GPP can be associated with systemic inflammation including fevers and/or hepatic, gastrointestinal, musculoskeletal, renal, or pulmonary involvement. The exact pathogenic mechanisms are not fully established. However, GPP is associated with a combination of genetic and environmental risk factors. Treatment options include using etanercept (a biologic) and cyclosporine, infliximab (a biologic) and methotrexate, or infliximab followed by etanercept. It is important to remember that the goals of treating GPP are to save a patient’s life and to reverse the generalized pustular psoriasis as quickly and effectively as possible.