The critically ill surgical patient is at high risk for the development of ICU-acquired infection. Normal mucosal defenses are breached by surgical incisions or by intravascular devices, urinary catheters, and endotracheal tubes. The integrity of the gastrointestinal epithelium is compromised by the lack of enteral nutrition and episodes of hypoperfusion, resulting in translocation of normal or disturbed enteric flora. The indigenous microbial flora, an important component of normal host defenses against invasive infection, is disrupted through the use of broad-spectrum antibiotics or by poorly understood influences associated with critical illness. Systemic immunity is altered, and multiple abnormalities of specific and nonspecific immune function can be documented. Infections acquired within the ICU are commonly caused by endogenous organisms of low intrinsic pathogenicity, and the contribution of these infections to ICU outcome is controversial. Diagnosis is established by directed investigations, focusing on surgical sites and invasive devices. Therapy is primarily physical (drainage of infected collections or removal of contaminated devices), and antimicrobial therapy should employ narrow-spectrum agents guided by the results of Gram stain and culture. The prevention of ICU-acquired infection is based on timely and definitive surgical therapy, judicious use of invasive devices and antibiotics, and early enteral feeding. Infection-control measures aimed at endogenous reservoirs show some preliminary promise for certain subsets of patients, but remain, at present, experimental.