The domestication of plants and animals marks one of the most significant transitions in human, and indeed global, history. Traditionally, study of the domestication process was the exclusive domain of archaeologists and agricultural scientists; today it is an increasingly multidisciplinary enterprise that has come to involve the skills of evolutionary biologists and geneticists. Although the application of new information sources and methodologies has dramatically transformed our ability to study and understand domestication, it has also generated increasingly large and complex datasets, the interpretation of which is not straightforward. In particular, challenges of equifinality, evolutionary variance, and emergence of unexpected or counter-intuitive patterns all face researchers attempting to infer past processes directly from patterns in data. We argue that explicit modeling approaches, drawing upon emerging methodologies in statistics and population genetics, provide a powerful means of addressing these limitations. Modeling also offers an approach to analyzing datasets that avoids conclusions steered by implicit biases, and makes possible the formal integration of different data types. Here we outline some of the modeling approaches most relevant to current problems in domestication research, and demonstrate the ways in which simulation modeling is beginning to reshape our understanding of the domestication process.T he emergence of agriculture beginning some 10,000 y ago marked more than a change in human patterns of subsistence. The beginnings of food production ushered in an era of radically new relationships between humans and other species, dramatic new evolutionary pressures, and fundamental transformations to the earth's biosphere. The evolutionary process of plant and animal domestication by humans led to morphological, physiological, behavioral, and genetic differentiation of a wide range of species from their wild progenitors (1, 2). The selection pressures that were placed on such species continue today, sometimes through direct genetic modification, and both the processes and their outcomes are accordingly of significant broader interest. Domestication is also part of a cultural evolutionary process (3, 4), and some human genes have evolved in response to cultural innovations (5-8), much as the genes of domesticated species have changed under the impact of human artificial selection. The study of domestication today is a multidisciplinary enterprise in which archaeologists and agricultural scientists have been joined by evolutionary biologists and population geneticists (2, 9).At least five major sets of questions tend to reoccur in the domestication literature. The first three are demographic: (i) When, where, and in how many geographic locations was a given species domesticated? (ii) What were the dispersal routes from the original domestication centers? (iii) To what extent did hybridization between domesticates and local wild relatives occur? The remaining questions relate to adaptation: (i...