Pronghorn (Antilocapra americana) are an endemic ungulate in western North America and occupy rangelands concurrently with domestic livestock. When rangelands are in healthy condition, there is little-to-no competition between pronghorn and domestic livestock. When rangeland health deteriorates, direct competition occurs when both compete for limited resources. Pronghorn are a highly mobile species that cope with challenging environmental conditions (both natural and human-imposed) through daily and seasonal movements to more favorable habitats. Maintaining healthy rangelands and rangeland connectivity will allow pronghorn to move freely and adapt to increased human disturbance. In addition, understanding the cumulative effects and identifying mitigation strategies of deleterious anthropogenic effects (i.e., habitat conversion, linear features, energy development, and climate changes) will help to ensure long-term persistence of pronghorn populations. Mitigation will be critical, in conjunction with expanded research efforts, to help gain a greater knowledge of the role of environmental conditions and anthropogenic disturbances on pronghorn fitness, persistence, and their ability to move across the land in response to an ever-changing landscape.