Virulence is one of a number of possible outcomes of host-microbe interacti
on. As such, microbial virulence is dependent on host factors, as exemplifi
ed by the pathogenicity of avirulent microbes in immunocompromised hosts an
d the lack of pathogenicity of virulent pathogens in immune hosts. Pathogen
-centered views of virulence assert that pathogens are distinguished from n
onpathogens by their expression of virulence factors. Although this concept
appears to apply to certain microbes that cause disease in normal hosts, i
t does not apply to most microbes that cause disease primarily in immunocom
promised hosts. The study of virulence is fraught with the paradox that vir
ulence, despite being a microbial characteristic, can only be expressed in
a susceptible host. Thus, the question "What is a pathogen?" begs the quest
ion, "What is the outcome of the host-microbe interaction?" We propose that
host damage provides a common denominator that translates into the differe
nt outcomes of host-microbe interaction.