Timely and appropriate antimicrobial therapy is an essential component of the management of intraabdominal infection. Over the past three decades, our ability to treat these infections optimally has been enhanced by an increased understanding of the underlying microbial pathogens, by the development of new antimicrobial agents, and by the completion of several well-controlled clinical trials that guide treatment. This article provides an overview of the approach to antimicrobial therapy in patients with intraabdominal infection. A literature review was performed to collect the information used in this article. Data were derived from experimental and clinical studies evaluating the microbiology and treatment of intraabdominal infections. Evidence from both animal studies and clinical trials supports the initiation of empiric antimicrobial therapy directed against Escherichia coli and other common members of the family Enterobacteriaceae, as well as the anaerobe Bacteroides fragilis. Based on this premise, the clinician is faced with a broad selection of possible single agents, as well as combinations of agents that fulfill these criteria. The factors involved in selecting a specific regimen include consideration of the antimicrobial spectrum of various agents, experimental animal studies evaluating their efficacy, and, importantly, efficacy in well-designed clinical trials. In addition, consideration of safety profiles, pharmacokinetics, and cost of specific pharmaceutical agents should be made when selecting a regimen. Antimicrobial therapy is an important component of the management of intraabdominal infection. The results of well-designed clinical trials evaluating various aspects of therapy should serve to guide treatment.