Gary Woodnutt – Diversa Corp., San Diego, CA, USAThere are multiple virulence factors that are required to initiate and maintain infection in the host. As many of these are external to the infecting cell, they provide clear target opportunities that would circumvent the need for cellular penetration. However, by definition, compounds that inhibit these targets would not kill the organism and thus many of the screening processes currently used will not be applicable. The difficulties associated with progressing targets of this type are discussed with some key examples of areas that might become clinical candidates in the near future. The suggestion that virulence inhibiting compounds might be less likely to generate resistance is intriguing but unproven. The lack of a clear path through regulatory bodies and the inability to test activity by traditional, and well accepted, clinical microbiology add to the complexity of achieving success with these novel interventions. However, as the clinical options for treatment of infectious disease are eroded by resistance the time might be ripe for exploiting these strategies.