Generalized pustular psoriasis (GPP) is a rare but severe inflammatory skin disease characterized by the eruption of widespread sterile pustules, often accompanied by systemic inflammation. Although GPP can coexist with plaque psoriasis, it is increasingly recognized as a distinct entity with unique clinicopathological, immunologic, and genetic features. The dysregulated IL-36 pathway, including mutations in the IL36RN gene, is implicated in GPP pathogenesis, providing a molecular basis for targeted therapies. Diagnosing GPP requires a comprehensive evaluation, including clinical presentation, potential triggers, patient history, histopathologic findings, and laboratory results. Disease severity must be assessed through both cutaneous symptoms and systemic involvement, as GPP flares can lead to life-threatening complications such as sepsis and multi-organ failure. Historically, GPP treatment primarily relied on therapies approved for plaque psoriasis, despite their limited specificity for this condition. Recent advances in understanding the molecular mechanisms of GPP, particularly the central role of interleukin-36 pathway, have led to the development of targeted therapies for this rare condition. Currently, spesolimab is the only therapy specifically approved for treating GPP flares in adolescents and adults, in both Europe and the United States of America. However, the management of GPP remains complex and challenging. This narrative review provides an overview of the epidemiology, pathophysiology, clinical features, comorbidities, and evolving therapeutic strategies for GPP.