Crop domestication represents a key interaction between nature and society. Indeed, human-mediated changes in the growing environment of organisms have greatly influenced their evolutionary trajectories. Perhaps, less explored is how crop evolution is influenced by ongoing domestication practices that are common in Mexico. Among the myriad plant species domesticated in the Mesoamerican center of crop origin, chili pepper is an excellent model for studying evolution under domestication. With over 60 cultivated varieties, gene flow with wild populations is common, and both wild and cultivated chili peppers are consumed. In this chapter, the social-natural history of Capsicum annuum is sketched, its domestication syndrome revisited, and progress unraveling its genetic underpinnings presented. The effect of the domestication gradient on ecological niche differentiation is discussed and its influence on genetic structuring assessed in combination with management systems that enhance/suppress gene flow. Furthermore, two case studies are explored. One addresses the experimental effects of temperature on phenotypic plasticity for wild and domesticated germplasm, and the other provides an ethnographic focus on traditional management techniques. Finally, the role of rural household economic units in furthering the evolution of chilies is detailed through local management practices in three illustrative examples from the states of Oaxaca and Puebla.