Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that is uncommon and can sometimes be associated with systemic diseases. The pathophysiology underlying this condition is poorly understood, although recent advances suggest that local cutaneous abnormalities and functionally abnormal neutrophils may trigger ongoing innate and adaptive immune system activity. PG remains a difficult condition to diagnose, mainly because it was previously seen as a diagnosis of exclusion, although newer diagnostic criteria have been proposed in order to overcome this. Furthermore, many patients do not respond to conventional therapy for PG once diagnosed, and experience persistence or worsening of their condition over time. The advent of immune targeted therapies, however, may represent a new treatment option for these patients. This review focuses on the clinical features and diagnosis of PG, as well as providing an update in our understanding of the pathophysiology and treatment options available for this debilitating condition.