Generalized pustular psoriasis (GPP) is a severe, life-threatening disease that represents a major therapeutic challenge. There is a lack of randomized controlled trials assessing the efficacy of various treatment options for GPP. TNFα inhibitors have proven to be effective and are increasingly used in this indication. In the current paper, we present two patients with GPP treated with infliximab (Ifx) and a literature review appraising currently available data on the use of Ifx in GPP. Case 1 was a 73-year-old woman with GPP who exhibited lack of treatment response or primary intolerance to standard therapeutic options (high-dose acitretin, methotrexate, cyclosporine A, and methylprednisolone). However, Ifx therapy combined with low-dose acitretin resulted in rapid and sustained resolution of skin lesions. Case 2 was a 60-year-old man with GPP and numerous comorbidities who was initially treated with Ifx in combination with methotrexate, with good treatment response for 9 months. Following an infection-induced flare of GPP at week 38, methotrexate was discontinued in favor of low-dose acitretin and Ifx continued. This regimen again resulted in rapid resolution of pustules. We present these cases to highlight the advantage of long-term Ifx therapy with low-dose acitretin in GPP.