Optimal virulence is an idea relating to the ecology of hosts and parasites. One definition of virulence is the host's parasite induced loss of fitness. The parasite's fitness is determined by its success in transmitting offsprings to other hosts. It stands to reason that the parasite, aiming to increase its fitness as much as possible will increase probability of transmission by increasing the number of offsprings produced. However, the host, being the parasite's resource and habitat in a way, suffers from this higher virulence. This might induce faster host death, and act against the parasite's fitness by reducing probability to encounter another host (killing the host too fast to allow for transmission). Thus, there is a natural force providing pressure on the parasite to "self-limit" virulence. The idea is, then, that there exists an equilibrium point of virulence, where parasite's fitness is highest. Any movement on the virulence axis, towards higher or lower virulence, will result in lower fitness for the parasite, and thus will be selected against.

At one time, the consensus was that over time, virulence moderated and parasitic relationships evolved toward symbiosis. This view was challenged by Paul Ewald. He explored the relationship between virulence and mode of transmission and came to the conclusion that virulence remains high in waterborne and vector-borne infections, such as cholera and Dengue. Cholera is spread through sewage and Dengue through mosquitos. In both cases, transmission does not depend on a mobile host. When it does, as in respiratory infections, the pathogen can only survive if it spares the host long enough to find a new host. At the same time, a pathogen that is too restrained will lose out in competition to a more aggressive strain that diverts more host resources to its own reproduction. Other epidemiologists have expanded on the idea of a tradeoff between costs and benefits of virulence. One factor is the time or distance between potential hosts. Ewald is convinced that the crowding of trench warfare is a major cause of the virulence of the 1918 influenza pandemic. Airplane travel, crowded factory farms and urbanization have all been suggested as possible sources of virulence. Another factor is the presence of multiple infections in a single host leading to increased competition among pathogens. In this situation, the host can survive only as long as it resists the most virulent strains. The advantage of a low virulence strategy becomes moot. Host susceptibility contributes to virulence. Once transmission occurs, the pathogen must establish an infection to continue. The more competent the host immune system, the less chance there is for the parasite to survive.It may require multiple transmission events to find a suitable host. During this time, the invader is dependent upon the survival of its current host. For this reason virulence thrives in a community with prevalent immune dysfunction and poor nutrition. Virulence weakens in a healthy population and as hosts acquire resistance. Good hygiene, nutrition and sanitation are all effective strategies against virulence.