The process of canine domestication represents certainly one of the most interesting questions that evolutionary biology aims to address. A “multiphase” view of this process is now accepted, with a first phase during which different groups of wolves were attracted by the anthropogenic niche and a second phase characterized by the gradual establishment of mutual relationships between wolves and humans. Here, we provide a review of dog (Canis familiaris) domestication, highlighting the ecological differences between dogs and wolves, analyzing the molecular mechanisms which seem to have influenced the affiliative behaviors first observed in Belyaev’s foxes, and describing the genetics of ancient European dogs. Then, we focus on three Mediterranean peninsulas (Balkan, Iberian and Italian), which together represent the main geographic area for studying canine domestication dynamics, as it has shaped the current genetic variability of dog populations, and where a well-defined European genetic structure was pinpointed through the analysis of uniparental genetic markers and their phylogeny.