Waterborne disease is estimated to cause about 10% of all diseases worldwide. However, related risk perceptions are not well understood, particularly in the developing world where waterborne disease is an enormous problem. We focus on understanding risk perceptions related to these issues in a region within northern Mexico. Our findings show how waterborne disease problems and solutions are understood in eight small communities along a highly contaminated river system. We found major differences in risk perceptions between health professionals, government officials, and lay citizens. Health professionals believed that a high level of human-waste-related risk existed within the region. Few officials and lay citizens shared this belief. In addition, few officials and lay citizens were aware of poor wastewater-management-related disease outbreaks and water contamination. Finally, aside from health professionals, a few interviewees understood the importance of basic hygiene and water treatment measures that could help to prevent disease. Our results add to the literature on environmentally-related risk perceptions in the developing world. We discuss recommendations for improving future human-wastewater-related risk communication within the region.