Background: Although guidelines and reviews have systematically evaluated diagnosis and surgical management of acute diverticulitis, they have focused only minimally on antibiotic selection for the treatment of this disease. We undertook a review of the literature to assess more clearly the use of specific antimicrobial agents in the treatment of patients with acute diverticulitis of the colon. Methods: A MEDLINE search was conducted to identify original research, review papers, and guidelines on the use of antimicrobial agents for the treatment of acute diverticulitis. Results: The general recommendation to use antibiotics with activity against common gram-negative and anaerobic pathogens has remained consistent. A number of single agents and combination regimens provide such activity. However, there is little evidence on which to base selection of specific antimicrobial regimens, and no regimen has demonstrated superiority. In general, episodes of diverticulitis severe enough to warrant hospitalization should be managed initially with intravenous antibiotics. Oral therapy can be used for outpatient treatment or when the patient's condition improves. There is a paucity of data regarding the optimal duration of antimicrobial therapy. Conclusions: Careful clinical studies are needed to evaluate better the antibiotic regimens for the treatment of acute diverticulitis. Until such studies are conducted, we are forced to rely on tradition, in vitro analyses, pharmacokinetic profiling, and indirect evidence from studies of complicated intra-abdominal infections to determine appropriate therapy for this disease.