 Pioderma gangrenosum, a rare inflammatory skin disorder characterized by neutrophil dysfunction, has no FDA-approved drug treatment and typically relies on traditional immunosuppressive medications. Biologic and small molecule therapies target specific pro-inflammatory mediators that underlie PG pathogenesis, making them a compelling topic for investigation in treating this disease. This review updates the use of biologic and small molecule medications for the treatment of PG and summarizes their clinical efficacy and pharmacology.