Dogs of different breeds can range remarkably in size, shape, and behavior, and yet they all carry essentially the same genome, making them a particularly fascinating model for genome plasticity. The recent release of the complete sequence of the dog genome provides an exciting new context in which to consider such variation. Twenty-six chapters written by experts in the field include various aspects of morphological and behavioral variation in dogs, their origins and domestication, and their unique value as a model system for many common but complex human diseases such as cancer, blindness, deafness, neurological diseases, and epilepsy.