We assume conservation lessons learnt from Southeast Asia adapted to the growing body of knowledge in oil palm impacts in Colombia, and adapt it to the Neotropical realm with a focus on mammals. Aspects of science, policy, and practice are reviewed. Colombia is the fourth largest producer of palm oil in the world with a growth of 42% in 2017, affecting its ecosystems and biodiversity. In order to prevent large mammal species erosion and decimation as has happened in SE Asia, the following lessons in zoning, infrastructure, harvest, monitoring, and research should be implemented. Native habitat is irreplaceable. New oil palm frontiers should occur in degraded ecosystems, with adequate governance and without requirement of new infrastructure. Roads favor hunting, logging, and disorganized human occupation. Plantations should conserve water bodies and forests to ensure connectivity and refuge for sensitive mammal species. Higher structural complexity with added plants is desired for a varied mammal species composition. Harvest should be done manually and crepuscular work hours should be avoided. How new oil palm frontiers are opened and developed will define the extent of alteration of natural mammal assemblages, the intensity of mesopredator release affecting other species from cascading trophic phenomenon and even the continuation of key large iconic herbivores and carnivores.