A total of 48,440 Enterobacteriaceae isolates collected consecutively from patients hospitalized in participant SENTRY Antimicrobial Surveillance Program sites in four international regions (Asia-Pacific, Europe, Latin America, and North America) were tested by reference broth microdilution method against the most commonly used antimicrobial agents. The most active compounds could be divided in 3 groups based on their spectrum of activity. The first group included meropenem and imipenem, with 99.9% susceptibilty (S) rates for the Enterobacteriaceae. The second group includes amikacin (97.3% S) and cefepime (97.2% S); and a third active group had a rank order of susceptibility of: gatifloxacin = levofloxacin (91.7% S) > ceftazidime (91.4% S) > ceftriaxone (91.2% S) > aztreonam (91.1% S) > gentamicin (90.6% S) > piperacillin/tazobactam = ciprofloxacin (90.5% susceptibility). These latter antimicrobial agents presented susceptibility rates of approximately 90% (89.8%-91.7%). Continued resistance surveillance by various programs remain necessary to monitor the in vitro effectiveness of antimicrobial agents currently used in clinical practice.