The seventh year of the Zyvox Annual Appraisal of Potency and Spectrum Program (2008) continues to monitor the in vitro activities of linezolid and comparator agents tested against Gram-positive pathogens in Latin America, Europe, Canada, and the Asia-Pacific region. Linezolid is an oxazolidinone approved for the treatment of vancomycin-resistant Enterococcus faecium infections, complicated skin and soft tissue infections, and nosocomial pneumonia caused by various Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA). Surveillance isolates were submitted from 64 medical centers (24 countries) for a total of 6121 strains. Each country was requested to send 200 consecutive isolates in 6 targeted pathogen categories to a central processing laboratory, except the United Kingdom, Japan, and China where more strains were processed (400, 400, and 800, respectively). Reference broth microdilution susceptibility testing methods were used to test the following organism groups: S. aureus (3240), coagulase-negative staphylococci (CoNS) (748), enterococci (864), Streptococcus pneumoniae (655), viridans group (297), and beta-hemolytic streptococci (317). Eight linezolid-resistant (LZD-R) isolates were detected in 7 countries (Italy [2], France, China, Brazil, Sweden, Germany, and United Kingdom) among the enterococci (Enterococcus faecalis [3] and E. faecium [2]) and CoNS (3 Staphylococcus epidermidis). Five LZD-R isolates contained 23S rRNA mutations (G2576T or G2447T), and 2 strains had undeterminable resistance mechanisms. One CoNS (Italy) contained the mobile cfr gene. Vancomycin-resistant enterococci rates ranged from 0.0% in several countries to 59.4% in Taiwan. All streptococci were linezolid susceptible (MIC(90), 1 microg/mL). In conclusion, the activity of linezolid remained uniform and stable across the sampled geographic regions studied when compared to the 2006 to 2007 results. Documented LZD-R remains rare (only 0.13% overall but highest for CoNS [0.41%] and enterococci [0.69%]) among the 24 countries sampled for the 6 different pathogen groups. Rates of clindamycin resistance and the frequency of MRSA varied by geographic region and between nations; therefore, like oxazolidinones, it requires continued surveillance for changing resistance patterns.