Clinical and Laboratory Standards Institute breakpoints for cefazolin against Enterobacteriaceae that were published in January 2010 have been revised by the Subcommittee on Antimicrobial Susceptibility Testing, based on the examination of recent data about in vitro activity, pharmacokinetic-pharmacodynamic characteristics and published clinical outcome studies. The new breakpoints, to be formally published in January 2011, have increased the minimum inhibitory concentration interpretive criteria by one 2-fold dilution, linked to an adult dosing schedule of 2 g every 8 h intravenously. Disk diffusion zone diameter correlates, shown to be impossible to define with the January 2010 interpretive criteria, have been able to be set for the new interpretive criteria. Diagnostic laboratories will continue to need to test cephalothin to predict susceptibility to the oral cephalosporins cefadroxil, cefpodoxime, cephalexin, and loracarbef.