Pyoderma gangrenosum (PG) shows features of autoimmune and autoinflammatory disorders. Genetic defects which affect the inflammasome, and in particular the NLRP3 zone, can cause an abnormal secretion of interleukin 1 (IL-1). IL-1 may be involved in clinical manifestation of certain (genetic) forms of PG. IL-1 receptor antagonists reduce the activity of IL-1α and IL-1β. Mutations in the PSTPIP1 gene have been identified in patients with pyogenic arthritis, pyoderma gangrenosum and acne syndrome. In patients with a pyoderma gangrenosum, acne, and suppurative hidradenitis syndrome these mutations cannot be found and the effect of IL-1 inhibition is questionable. Another upcoming opportunity is targeted therapy by tumor necrosis factor-alfa inhibitors in steroid-resistant patients. This review has been focused on (1) the modern pathogenetic concepts, (2) the currently accepted criteria for differentiating the disease, (3) the target therapy and (4) valuable advice to the clinicians regarding a number of medicaments capable of aggravating or inducing the PG.