Today, populations of eastern oysters, Crassostrea virginica, are commonly limited by disease mortality. Resistance to MSX disease has developed in a number of cases, but the development of resistance to Dermo disease would appear to be limited, despite the high mortality rates and frequency of epizootics. Can aspects of the host's genetics or population dynamics limit the response to the disease despite the apparent opportunity afforded by alleles conferring disease resistance or tolerance? To answer this question, we use a gene-based population dynamics model, configured for C. virginica, to simulate the development of disease resistance using mortality as the agent of selection. Simulated populations were exposed to 4 levels of mortality covering the range in mortality observed in Delaware Bay in the 1990s. In each case, disease resistance increased in the simulated population over time, normally proportional to the increase in mortality rate imposed by the disease. However, simulations show that the population responds even at its most rapid rate on multidecadal to half-century timescales. As the mortality rate declines with increasing disease resistance, the rate of further improvement in disease resistance likewise declines. Thus, disease resistance develops over decadal timescales at a 40%-per-year mortality rate, but, as mortality rate falls to 25% per year, the rate of further development of disease resistance extends to half-century timescales. The discouraging profundity is that a mortality rate of 25% per year, yielding a rate of selection profoundly slow, is still very high. In northern climes, significant decrements in oyster abundance will occur. Evidence from fisheries retrospectives suggests that oysters cannot withstand a constant removal at this scale without compromising population integrity noticeably. So, a mortality rate that grievously limits the development of disease resistance still sorely strains the species' ability to maintain a vibrant population necessary to its long-term survival.