Why do only certain microbes have the capacity to be virulent, and why are certain microbes virulent only in certain hosts? These fundamental questions have shaped and directed the thinking of microbiologists and the field of microbial pathogenesis since the germ theory of disease was proposed in the late 19th century. The germ theory gave rise to the prevailing view that there are fundamental differences between pathogenic and nonpathogenic microbes. This view, which regards virulence as a microbial characteristic, is supported by the observation that certain microbes require specific factors, such as toxins and capsules, for animal virulence. However, almost since it was first put forth that pathogens and nonpathogens are fundamentally different, there have been exceptions and challenges to this view. The demonstration that animal and/or in vitro passage can alter virulence illustrated that virulence is not necessarily a stable or invariant trait. Then, the 20th-century emergence of commensal microbes that were previously considered to be avirulent, such as Candida albicans (7) and Staphylococcus epidermidis (40), as clinically relevant pathogens provided clear evidence that virulence can be a function of the immune status of the host. For microbes that cause disease at one time but not another, the determinant of disease is often a change in the host that alters the host-microbe interaction. Hence, while virulence is a microbial property, it is expressed only in a susceptible host (4). Given that the outcome of microbial infection is often a function of the immune status of the host and that a susceptible host is required for microbial virulence, it makes sense to categorize microbial pathogens based on how they are acquired. There are two basic types of acquisition. One type encompasses microbes that are acquired from other living hosts, including those of the same or different species, eg, insects or protozoa. The other type encompasses microbes that are acquired from the environment, though it may contain the remains of formerly living species, such as decaying vegetation.