Pyoderma gangrenosum (PG) is a rare, painful, inflammatory skin condition characterized by rapidly spreading ulcers. Its exact pathophysiology remains unclear, though it is often considered part of the neutrophilic dermatoses. Treatment is challenging due to the lack of standardized guidelines, with current approaches focusing on immunosuppressive and immunomodulatory therapies. Recent studies have shown promising results with biologic drugs and small molecules used for coexisting conditions. This review summarizes the current understanding of PG's pathophysiology and treatment options, aiming to improve awareness and management of this rare disease. PG is associated with various systemic conditions, including inflammatory bowel disease, rheumatoid arthritis, and hematological malignancies. Six clinical variants of PG exist, with ulcerative PG being the most common. PG can occur on various body parts, including the lower extremities, peristomal areas, and postoperative wounds. The disease is more prevalent in women and typically affects individuals around the age of 50. The pathophysiology of PG involves complex interactions between innate and adaptive immunity, with a key role for neutrophils. Genetic factors and immune dysregulation contribute to the development of PG. Cytokines such as IL-1β, IL-8, IL-17, and TNF-α play significant roles in the inflammatory process. PG can be triggered or exacerbated by trauma, leading to the release of inflammatory mediators. Treatment options include wound management, topical therapies, intralesional injections, and systemic immunosuppressants. Corticosteroids, cyclosporine A, and biologic drugs like TNF-α inhibitors (infliximab, adalimumab) are commonly used. Other immunosuppressants, including methotrexate, azathioprine, and IL-17 inhibitors, have also shown efficacy. Newer therapies, such as JAK inhibitors and IL-36 inhibitors, are being explored for their potential in PG treatment. Despite advances, PG remains a challenging condition to treat, with limited evidence-based guidelines. Future research aims to develop targeted therapies based on a deeper understanding of PG's pathophysiology. Ongoing clinical trials may introduce new treatment options, such as spesolimab and vilobelimab, offering hope for more effective management of this rare disease.Pyoderma gangrenosum (PG) is a rare, painful, inflammatory skin condition characterized by rapidly spreading ulcers. Its exact pathophysiology remains unclear, though it is often considered part of the neutrophilic dermatoses. Treatment is challenging due to the lack of standardized guidelines, with current approaches focusing on immunosuppressive and immunomodulatory therapies. Recent studies have shown promising results with biologic drugs and small molecules used for coexisting conditions. This review summarizes the current understanding of PG's pathophysiology and treatment options, aiming to improve awareness and management of this rare disease. PG is associated with various systemic conditions, including inflammatory bowel disease, rheumatoid arthritis, and hematological malignancies. Six clinical variants of PG exist, with ulcerative PG being the most common. PG can occur on various body parts, including the lower extremities, peristomal areas, and postoperative wounds. The disease is more prevalent in women and typically affects individuals around the age of 50. The pathophysiology of PG involves complex interactions between innate and adaptive immunity, with a key role for neutrophils. Genetic factors and immune dysregulation contribute to the development of PG. Cytokines such as IL-1β, IL-8, IL-17, and TNF-α play significant roles in the inflammatory process. PG can be triggered or exacerbated by trauma, leading to the release of inflammatory mediators. Treatment options include wound management, topical therapies, intralesional injections, and systemic immunosuppressants. Corticosteroids, cyclosporine A, and biologic drugs like TNF-α inhibitors (infliximab, adalimumab) are commonly used. Other immunosuppressants, including methotrexate, azathioprine, and IL-17 inhibitors, have also shown efficacy. Newer therapies, such as JAK inhibitors and IL-36 inhibitors, are being explored for their potential in PG treatment. Despite advances, PG remains a challenging condition to treat, with limited evidence-based guidelines. Future research aims to develop targeted therapies based on a deeper understanding of PG's pathophysiology. Ongoing clinical trials may introduce new treatment options, such as spesolimab and vilobelimab, offering hope for more effective management of this rare disease.