The domestication of plants and animals is a key transition in human history, and its profound and continuing impacts are the focus of a broad range of transdisciplinary research spanning the physical, biological, and social sciences. Three central aspects of domestication that cut across and unify this diverse array of research perspectives are addressed here. Domestication is defined as a distinctive coevolutionary, mutualistic relationship between domesticator and domesticate and distinguished from related but ultimately different processes of resource management and agriculture. The relative utility of genetic, phenotypic, plastic, and contextual markers of evolving domesticatory relationships is discussed. Causal factors are considered, and two leading explanatory frameworks for initial domestication of plants and animals, one grounded in optimal foraging theory and the other in niche-construction theory, are compared.