Pyoderma Gangrenosum is a rare neutrophilic dermatosis with multiple different clinical presentations and associated comorbidities. Historically, it has been a challenging disorder to diagnose, as it is difficult to establish this condition based on a clinical presentation. Recently, several studies have attempted to define the prevalence of clinical manifestations of PG in order to improve diagnostic accuracy leading to the development of new diagnostic criteria rather than the traditional approach of a diagnosis of exclusion. Moreover, new biologic treatment modalities have been introduced. Objective: In this study, we aimed to evaluate the management and diagnostic approach of pyoderma gangrenosum in the emergency department. Methodology: PubMed database was used for articles selection, and the following keys were used in the mesh ((“Pyoderma Gangrenosum "[Mesh]). Conclusion: There is no diagnostic gold standard. However, PARACELSUS has been adopted as a novel diagnostic tool. Although the pathophysiology of PG is still incompletely understood. The discovery of new inflammatory cytokines and signal cascades has led to the development of a novel biologic therapy. However, significant research is needed in biologic therapy as it is difficult to assess long-term efficacy, adverse events, and remission rates as outcome measures for PG.