Until recently, biologists were unable to explain the fact that pathogens—disease-causing parasites—have evolved to incapacitate, and often overwhelm, their hosts. Such behavior is at odds with the prevailing view of host-parasite relations—that, in general, host and parasite ultimately develop a benign coexistence. This view is based on the idea that parasites that do not harm their hosts have the best chance for long-term survival: they thrive because their hosts thrive. Some biologists, however, recently have suggested that if a pathogen reproduced so extensively as to cause its host to become gravely sick, it could still achieve evolutionary success if its replication led to a level of transmission into new hosts that exceeded the loss of pathogens resulting from the host's incapacitation. This scenario suggests that even death-causing pathogens can achieve evolutionary success.

One implication of this perspective is that a pathogen's virulence—its capacity to overcome a host's defenses and incapacitate it—is a function of its mode of transmission. For example, rhinoviruses, which cause the common cold, require physical proximity for transmission to occur. If a rhinovirus reproduces so extensively in a solitary host that the host is too unwell to leave home for a day, the thousands of new rhinoviruses produced that day will die before they can be transmitted. So, because it is transmitted directly, the common cold is unlikely to disable its victims.

The opposite can occur when pathogens are transported by a vector—an organism that can carry and transmit an infectious agent. If, for example, a pathogen capable of being transported by a mosquito reproduces so extensively that its human host is immobilized, it can still pass along its genes if a mosquito bites the host and transmits this dose to the next human it bites. In such circumstances the virulence is likely to be more severe, because the pathogen has reproduced to such concentration in the host that the mosquito obtains a high dose of the pathogen, increasing the level of transmission to new hosts.

While medical literature generally supports the hypothesis that vector-borne pathogens tend to be more virulent than directly transmitted pathogens—witness the lethal nature of malaria, yellow fever, typhus, and sleeping sickness, all carried by biting insects—a few directly transmitted pathogens such as diphtheria and tuberculosis bacteria can be just as lethal. Scientists call these "sit and wait" pathogens, because they are able to remain alive outside their hosts until a new host comes along, without relying on a vector. Indeed, the endurance of these pathogens, many of which can survive externally for weeks or months before transmission into a new host—compared, for instance, to an average rhinovirus life span of hours—makes them among the most dangerous of all pathogens.