The dynamic frontier-making in Colombia's Amazon department of Caquetá is the focus of this article. Since the mid-nineteenth century, booms and busts of commodity production have been associated with violent struggles as actors have challenged pre-existing orders and authorities. At different times, the area has been controlled by the Catholic Church, the Colombian state, FARC and paramilitary groups, following the different boom-and-bust cycles of commodity production. We use this case to theorise on the general mechanisms behind frontier-making. Reading the frontier literature through the lens of the coloniality of power, we draw four interrelated categories to access frontier-making analytically: commodity production, dispossession, hegemon, and subjectivities. These are used to explain six distinct periods in the political economy of Caquetá and its spatial reconfigurations. We argue that current issues of distrust on the state, violence, and land grabbing, are best understood as part of a historical continuum of multiple actors keeping the area as a frontier space.