Fluconazole in vitro susceptibility test results determined by the CLSI M44-A disk diffusion method for 11,240 isolates of noncandidal yeasts were collected from 134 study sites in 40 countries from June 1997 through December 2007. Data were collected for 8,717 yeast isolates tested with voriconazole from 2001 through 2007. A total of 22 different species/organism groups were isolated, of which Cryptococcus neoformans was the most common (31.2% of all isolates). Overall, Cryptococcus (32.9%), Saccharomyces (11.7%), Trichosporon (10.6%), and Rhodotorula (4.1%) were the most commonly identified genera. The overall percentages of isolates in each category (susceptible, susceptible dose dependent, and resistant) were 78.0%, 9.5%, and 12.5% and 92.7%, 2.3%, and 5.0% for fluconazole and voriconazole, respectively. Less than 30% of fluconazoleresistant isolates of Cryptococcus spp., Cryptococcus albidus, Cryptococcus laurentii, Trichosporon beigelii/Trichosporon cutaneum, Rhodotorula spp., Rhodotorula rubra/Rhodotorula mucilaginosa, and Rhodotorula glutinis remained susceptible to voriconazole. Emerging resistance to fluconazole was documented among isolates of C. neoformans from the Asia-Pacific, Africa/Middle East, and Latin American regions but not among isolates from Europe or North America. This survey documents the continuing broad spectrum of activity of voriconazole against opportunistic yeast pathogens but identifies several of the less common species with decreased azole susceptibility. These organisms may pose a future threat to optimal antifungal therapy and emphasize the importance of prompt and accurate species identification.Although the majority of infections caused by yeasts are due to Candida (46,54,55,57), there are other yeast genera that may be considered to be "true pathogens" (i.e., Cryptococcus neoformans) or opportunists (e.g., Saccharomyces, Trichosporon, and Rhodotorula) that have taken advantage of immunocompromising conditions, indwelling devices, and broadspectrum antimicrobial use to colonize and infect at-risk patients (6, 7, 20, 26, 33, 39, 46, 55-57, 61, 62). Life-threatening infections caused by these less common fungi pose difficult management issues (1,7,55,61,62).Our knowledge of the epidemiology and antifungal susceptibilities of both Candida and C. neoformans has been enhanced through national, regional, and global surveillance (4,7,8,10,26,27,40,54,56,57,66); however, the same cannot be said for the other opportunistic yeast pathogens (46,55). Among the few surveillance programs that have monitored infection and resistance associated with noncandidal yeasts (15,21,(56)(57)(58), only the ARTEMIS Global Antifungal Surveillance Program has tracked this disparate group of organisms in a program that is both longitudinal and global in scope (29,51,56).The ARTEMIS program employs standardized Clinical Laboratory Standards Institute (CLSI) methods used for "routine" testing of fluconazole and voriconazole in participating laboratories (disk diffusion), uses electronic data capture and ...