Treatment of patients with complicated intra-abdominal infections involves antimicrobial therapy, generally in conjunction with an interventional procedure to control the source of the infection. Antimicrobial regimens effective against common gram-negative and anaerobic enteric pathogens are the mainstay of therapy. For patients with community-acquired intra-abdominal infections, efficacy is comparable among the various single-agent or combination regimens recommended for therapy. Narrower-spectrum antimicrobial agents with a low potential for iatrogenic complications are appropriate for these patients. Patients with nosocomially-acquired, intra-abdominal infections are more likely to harbor resistant pathogens. Inadequate empiric antimicrobial therapy is associated with treatment failure and death. Therefore, broader spectrum antimicrobial regimens are recommended for these patients. In addition to coverage of more resistant gram-negative bacilli and anaerobes, use of agents effective against enterococci, resistant staphylococci and Candida should be considered. De-escalation of an initially broad antimicrobial regimen should be undertaken once definitive culture results are available.