This paper broadly discusses the role of the natural resource base of Laos and northeast Thailand in shaping the human occupation of this important region over millennia. Examples are drawn from different materials utilized by human occupants from the early to later Holocene to illustrate how changing technological systems incorporated the region’s resources into their technological choices. As one example, plate tectonics created a dispersed and diversified metal ore resource landscape that shaped how metals were incorporated into metal age economies of the region. Minerology studies of ceramics from different tributary systems are beginning to show where prehistoric pottery was made and patterns by which it was exchanged. Variation in lithic raw materials by site and river basin can also illuminate networks of interaction. While such studies are at present nascent, their potential for illuminating the region’s ancient societies is vast.