Pyoderma gangrenosum (PG) is an ulcerative neutrophilic dermatosis seen in 1-5% of patients with inflammatory bowel disease (IBD). The pathogenesis of PG remains unclear, but may be related to abnormal T-cell responses and production of tumor necrosis factor (TNF)-alpha, a powerful proinflammatory cytokine. Although their use is not supported by appropriately controlled trials, corticosteroids and systemic immunosuppressants are the classical cornerstones of treatment of PG, against which they have a nonspecific effect. Successful curative or symptomatic treatment of associated disorders may lead to an improvement in PG. A new era for the management of chronic inflammatory disease began with the advent of biotherapies and particularly anti-TNFalpha therapy, which allows for a specific intervention in the immune cascade. Anti-TNFalpha therapy has improved and broadened the therapeutic options for IBD and, therefore, has brought new perspectives to management of the extra-intestinal manifestations of this disorder, including PG. To date, infliximab, etanercept, and adalimumab have been used in the treatment of PG. Published data have demonstrated that infliximab is highly effective in the treatment of PG, whether associated with IBD or not. This treatment is generally well tolerated, even as long-term therapy. However, rare and serious complications have been reported. Although infliximab is a costly drug, its use should be considered for patients with PG and particularly with corticosteroid-refractory PG associated with IBD. Additional comparative long-term studies are needed to determine the long-term efficacy and safety of anti-TNFalpha therapy and define its role in the management of PG, with or without accompanying IBD.