Understanding how Indigenous populations perceive HIV/AIDS is of high relevance for the implementation of culturally appropriate interventions. The study analyzed the ways in which Indigenous Wayuu communities of Colombia socially perceive and respond to HIV/AIDS from their sociocultural realities and their knowledge of the illness. It analyzed qualitative data from 9 focus groups and 29 semi-structured interviews. The Wayuu think of HIV/AIDS as “the illness”, that it is incurable, fatal, transmitted from alijunas (non Wayuu), and beyond their understanding. They seem to perceive HIV/AIDS similarly to the ways Western societies perceived unknown or misunderstood epidemics in the past.