Enterococci are an increasingly important cause of nosocomial infections. While the clinical impact of enterococci in cases of bacteremia and super-infections in selected patient populations has been well-established, their role as primary pathogens in polymicrobial intra-abdominal infections remains controversial. While it has been suggested that the presence of enterococci increases the rate of infectious post-operative complication, it has also been demonstrated that polymicrobial intra-abdominal infections involving enterococci can be treated successfully with appropriate surgical drainage and antibiotics, such as cephalosporins, that are not active against enterococci. Therefore, the question arises of whether or not antibiotic coverage against enterococci should be included in the empirical treatment of peritonitis in certain high-risk patient populations. An extensive literature review revealed some evidence arguing in favour of using empirical therapy with enterococcal coverage for intra-abdominal infections in the following cases: (i) immunocompromised patients with nosocomial, post-operative peritonitis; (ii) patients with severe sepsis of abdominal origin who have previously received cephalosporins and other broad-spectrum antibiotics selecting for Enterococcus spp.; (iii) patients with peritonitis and valvular heart disease or prosthetic intravascular material, which place them at high risk of endocarditis. The ideal therapeutic regimen for these high-risk patients remains to be determined, but empirical therapy directed against enterococci should be considered.