In the wake of seminal work by Dobzhansky and Muller, hybrid dysfunction is usually attributed to incompatible mutations in different genes arising in different populations. This Dobzhansky-Muller (D-M) model is among the most important contributions of theoretical population genetics. Here I make formal connections between the D-M model and the quantitative genetic interpretation of hybrid dysfunction as a combination of additive, dominance, and epistatic effects. Concerns over conceptual differences between the two approaches are unwarranted; the D-M model can be expressed as a special case of the statistical model developed for line-cross analysis in quantitative genetics. This unified theoretical framework encourages application of quantitative genetic methods to the study of speciation.