Pyoderma gangrenosum (PG) is a rare inflammatory dermatological disorder characterized by painful, aseptic ulcers that rapidly spread peripherally. The pathophysiology of PG is not fully understood but is often considered part of the spectrum of neutrophilic dermatoses. Treatment remains challenging due to the lack of generally accepted therapeutic guidelines. Current treatments focus on limiting inflammation through immunosuppressive and immunomodulatory therapies. Recent reports indicate successful use of biologic drugs and small molecules for coexisting diseases, leading to ulcer healing. This review summarizes recent discoveries about the pathophysiology of PG and presents treatment options to improve awareness and management of this rare condition. Key aspects include the role of neutrophils, T cells, inflammasomes, and genetic predispositions in PG pathogenesis. Treatment options range from wound management, topical therapies, intralesional therapies, and systemic therapies such as corticosteroids, cyclosporine A, mycophenolate mofetil, methotrexate, azathioprine, and immunosuppressive antibiotics. Biologic drugs like TNF-α inhibitors (infliximab, adalimumab), IL-1 antagonists (canakinumab, anakinra), IL-17 inhibitors (secukinumab, ixekizumab), and IL-23 inhibitors (guselkumab, tildrakizumab) have shown promise in treating PG. Future directions include targeted therapies such as Janus kinase inhibitors (JAKi) and novel drugs like spesolimab and vilobelimab. Collaborative efforts are essential for advancing research and improving PG management.Pyoderma gangrenosum (PG) is a rare inflammatory dermatological disorder characterized by painful, aseptic ulcers that rapidly spread peripherally. The pathophysiology of PG is not fully understood but is often considered part of the spectrum of neutrophilic dermatoses. Treatment remains challenging due to the lack of generally accepted therapeutic guidelines. Current treatments focus on limiting inflammation through immunosuppressive and immunomodulatory therapies. Recent reports indicate successful use of biologic drugs and small molecules for coexisting diseases, leading to ulcer healing. This review summarizes recent discoveries about the pathophysiology of PG and presents treatment options to improve awareness and management of this rare condition. Key aspects include the role of neutrophils, T cells, inflammasomes, and genetic predispositions in PG pathogenesis. Treatment options range from wound management, topical therapies, intralesional therapies, and systemic therapies such as corticosteroids, cyclosporine A, mycophenolate mofetil, methotrexate, azathioprine, and immunosuppressive antibiotics. Biologic drugs like TNF-α inhibitors (infliximab, adalimumab), IL-1 antagonists (canakinumab, anakinra), IL-17 inhibitors (secukinumab, ixekizumab), and IL-23 inhibitors (guselkumab, tildrakizumab) have shown promise in treating PG. Future directions include targeted therapies such as Janus kinase inhibitors (JAKi) and novel drugs like spesolimab and vilobelimab. Collaborative efforts are essential for advancing research and improving PG management.