It is difficult to overstate the cultural and biological impacts that the domestication of plants and animals has had on our species. Fundamental questions regarding where, when, and how many times domestication took place have been of primary interest within a wide range of academic disciplines. Within the last two decades, the advent of new archaeological and genetic techniques has revolutionized our understanding of the pattern and process of domestication and agricultural origins that led to our modern way of life. In the spring of 2011, 25 scholars with a central interest in domestication representing the fields of genetics, archaeobotany, zooarchaeology, geoarchaeology, and archaeology met at the National Evolutionary Synthesis Center to discuss recent domestication research progress and identify challenges for the future. In this introduction to the resulting Special Feature, we present the state of the art in the field by discussing what is known about the spatial and temporal patterns of domestication, and controversies surrounding the speed, intentionality, and evolutionary aspects of the domestication process. We then highlight three key challenges for future research. We conclude by arguing that although recent progress has been impressive, the next decade will yield even more substantial insights not only into how domestication took place, but also when and where it did, and where and why it did not.The domestication of plants and animals was one of the most significant cultural and evolutionary transitions in the ∼200,000-y history of our species. Investigating when, where, and how domestication took place is therefore crucial for understanding the roots of complex societies. Domestication research is equally important to scholars from a wide range of disciplines, from evolutionary biology to sustainability science (1, 2). Research into both the process and spatiotemporal origins of domestication has accelerated significantly over the past decade through archaeological research, advances in DNA/ RNA sequencing technology, and methods used to recover and formally identify changes in interactions among plants and animals leading to domestication (2-4). In the spring of 2011, 25 scholars with a central interest in domestication and representing the fields of genetics, archaeobotany, zooarchaeology, geoarchaeology, and archaeology met at the National Evolutionary Synthesis Center to discuss recent progress in domestication research and identify challenges for the future. Our goal was to begin reconsidering plant and animal domestication within an integrated evolutionary and cultural framework that takes into account not just new genetic and archaeological data, but also ideas related to epigenetics, plasticity, geneby-environment interactions, gene-culture coevolution, and niche construction. Each of these concepts is relevant to understanding phenotypic change, heritability, and selection, and they are all fundamental components of the New Biology (5) and Expanded Modern Evolutionary Synthesis (6).