Wild populations face threats both from deterministic factors, e.g., habitat loss, overexploitation, pollution, and introduced species, and from stochastic events of a demographic, genetic, and environmental nature, including catastrophes. Inbreeding reduces reproductive fitness in naturally outbreeding species, but its role in extinctions of wild populations is controversial. To evaluate critically the role of inbreeding in extinction, we conducted realistic population viability analyses of 20 threatened species, with and without inbreeding depression, using initial population sizes of 50, 250, and 1000. Inbreeding markedly decreased median times to extinction by 28.5, 30.5, and 25% for initial populations of 50, 250, and 1000, respectively, and the impacts were similar across major taxa. The major variable explaining differences among species was initial population growth rate, whereas the impact of inbreeding was least in species with negative growth rates. These results demonstrate that the prospects for survival of threatened species will usually be seriously overestimated if genetic factors are disregarded, and that inappropriate recovery plans may be instituted if inbreeding depression is ignored.