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In this paper, both the empirical and theoretical genetic aspects of human-mediated introgressive hybridization are reviewed in terms of their association with the breakdown of postzygotic isolating mechanisms. I also compare several simulation models with an ecological or genetic focus that are relevant to the prediction and risk assessment of genetic extinction due to hybridization. One barrier to devising comprehensive risk assessment frameworks is a lack of sufficient population genetic studies that associate introgressive hybridization with specific isolating mechanisms. A gametic model based on multilocus underdominant fitness is one of the best genetic models for introgressive hybridization because it explicitly incorporates the postzygotic isolating mechanism known as Dobzhansky-Muller genetic incompatibility.