A systematic approach is presented for the patient with antibiotic failure. Noninfectious mimics of infection and nontreatable infections must first be excluded. Then,, the clinician must identify those patients who have responded but have a surgical component of their infection or have complications separate from their initial infection. Such complications could include drug fever, phlebitis, decubiti, urinary tract infection, aspiration, and pulmonary embolism. Other patients may deteriorate clinically because of incorrect antibiotic coverage, failure of antibiotic to reach the site of infection, local inactivation of antibiotic, paradoxical response, immune compromise, or because they have reached the point of no return.